Cutaneous Biophysical Characteristics of

Melasma

by

Dong Jun Lee

Major in Medicine

Department of Medical Sciences

The Graduate School, Ajou University

Cutaneous Biophysical Characteristics of

Melasma

by

Dong Jun Lee

A Dissertation Submitted to The Graduate School of Ajou

University in Partial Fulfillment of the Requirements for the

Degree of Master of Medicine

Supervised by

Hee Young Kang, M.D., Ph.D.

Major in Medicine

Department of Medical Sciences

The Graduate School, Ajou University

August, 2011

This certifies that the dissertation

of Dong Jun Lee is approved.

SUPERVISORY COMMITTEE

Hee Young Kang

Eun-So Lee

You Chan Kim

The Graduate School, Ajou University

June 23rd, 2011

감사

본 논 시작에 끝 지 심 양면 도움 주시고 지도

조언 아끼지 않 셨 지도 이신 강희 님께 감사를

드립니다. 또한 좋 연구를 할 있도 부족한 가 많 가르침

주시고 격 를 주신 이 소 님과 찬 님께도 감사

마 합니다.

그리고 연구 간 동안 도움 주신 피부 과학 실 모든

생님들과 실험 여러 과 도 주신 IEC Korea Skin Research

Center 하재 생님, 이 생님과 조직 염색과 분 도 주신

배 생님께 감사 드립니다. 언 나 아낌 없는 사랑 지원해

주시는 부모님, 가족들에게도 감사 마 합니다.

2011 6 월

자씀

i

- ABSTRACT-

Cutaneous Biophysical Characteristics of Melasma

Background: Melasma is characterized by increased pigmentation and photodamaged

skin. These features suggest that melasma patients might have a significant impact on

cutaneous biophysical characteristics.

Objective: The cutaneous biophysical characteristics in melasma were investigated.

Methods: A total of 16 Korean volunteers with melasma were enrolled. The melanin

index/erythema index, stratum corneum (SC) hydration, sebum content, and

transepidermal water loss (TEWL) were measured and compared between lesional and

perilesional normal skin. The TEWL was re-measured immediately and 5 hours after tape

stripping to investigate SC integrity and barrier recovery rate. The sebum content was

measured at 30 minutes and 5 hours after degreasing by facial washing to estimate the

sebum excretion rate. Skin biopsy was performed in 11 volunteers to measure the SC

thickness and to study the expression of lipid metabolism associated genes such as

peroxisome proliferator-activated receptor alpha (PPAR-α), and arachidonate 15-

lipoxygenase, type B (ALOX15B).

Results: The melanin index, erythema index, and SC hydration were significantly higher

in lesional skin compared to nonlesional skin, whereas the measurement of basal TEWL

showed no significant difference. However, the increased rate of TEWL after tape-

stripping was significant higher in lesional skin compared to nonlesional skin. Also,

ii

barrier recovery rate of lesional skin was significant delayed. The melanin index was

found to be inversely correlated with the barrier recovery rate. There was no significant

difference between the basal sebum content and the sebum excretion rate. The expression

between PPAR-α and ALOX15B was not significantly different, whereas SC thickness

was reduced in lesional skin, which showed correlation with the barrier recovery rate.

Conclusions: Melasma skin showed a normal hydration state and sebaceous gland

activity. However, the SC integrity and barrier function were impaired in lesional skin of

melasma. The SC thickness was reduced in lesional skin, and it positively correlated with

the barrier recovery rate. These results suggest that improving SC function should be

considered in treating melasma.

Keywords: Melasma, Stratum corneum, Barrier function, TEWL

iii

TABLE OF CONTENTS

ABSTARCT ·············································································································· i

TABLE OF CONTENTS ························································································· iii

LIST OF FIGURES ································································································· iv

LIST OF TABLES ···································································································· v

I. INTRODUCTION ································································································· 1

II. MATERIALS AND METHODS ·········································································· 3

A. Subjects ·········································································································· 3

B. Measurement of biophysical properties ··························································· 5

C. Measurement of stratum corneum thickness and immunohistochemistry ·········· 5

D. Statistical analysis ···························································································· 6

III. RESULTS ··········································································································· 8

A. Melanin index and erythema index ····································································· 8

B. Basal stratum corneum properties ····································································· 10

C. Epidermal permeability barrier function ···························································· 11

D. Sebum content ·································································································· 13

E. Expressions of PPAR-α and ALOX15B and SC thickness ································· 14

IV. DISCUSSION ··································································································· 17

V. CONCLUSION ·································································································· 22

REFERENCES ······································································································· 23

국 요약 ················································································································ 26

iv

LIST OF FIGURES

Fig. 1. Melanin/Erythema index ·················································································· 8

Fig. 2. Stratum corneum capacitance ········································································· 10

Fig. 3. Basal TEWL ·································································································· 11

Fig. 4. Barrier recovery rate ······················································································ 12

Fig. 5. Correlation between melanin index and barrier recovery rate ·························· 13

Fig. 6. Sebum contents ······························································································ 14

Fig. 7. Expressions of PPAR-α and ALOX15B and stratum corneum thickness ········· 15

Fig. 8. Stratum corneum thickness and correlation with barrier recovery rate ············· 16

v

LIST OF TABLES

Table 1. General characteristics of volunteers ····························································· 4

- 1 -

I. INTRODUCTION

Melasma is a common acquired hyperpigmentary disorder characterized by

irregular light to dark brown macules and patches on sun-exposed skin.(Kang et al., 2002) A

major histopathological feature of melasma is an increased epidermal pigmentation. Melanin

is concentrated in the basal layer but also distributed throughout the epidermis. It has been

thought that skin pigmentation is associated with multiple cutaneous functions. Stratum

corneum (SC) in black skin contains more cell layers and greater electrical resistance and

requires more tape strips to remove it than that of white skin, suggesting better intercellular

cohesion in black skin.(Berardesca and Maibach, 1996) Moreover, epidermal barrier function

is different between blacks and white skin, although the results are inconclusive. Darker skin

has been shown to recover faster after barrier damage.(Reed et al., 1995) Whereas,

Kompaore et al.(Kompaore et al., 1993) found significant higher transepidermal water loss

(TEWL) after stripping in blacks and Asians than in whites. These findings suggest that

lesional skin of melasma may have different biophysical characteristics compare to non-

lesional skin.

Additional distinguishing histological characteristics of melasma are the features of

photodamaged skin. It is reported that Melasma lesions show a higher degree of UV-induced

damage, like solar elastosis and increased vascularity.(Kang et al., 2002; Kim et al., 2007;

Hernandez-Barrera et al., 2008) Photodamaged skin has been thought to have modified

cutaneous functions. Barrier recovery is delayed in photoaged skin as compared to

chronologically aged skin.(Reed et al., 1997) Moreover, recently we found that most lipid

- 2 -

metabolism-associated genes such as peroxisome proliferator-activated receptor alpha

(PPARA) and arachidonate 15-lipoxygenase, type B (ALOX15B) were down-regulated,

accompanying a delayed barrier recovery rate in lesional skin.(Kang et al., 2011) These

findings suggest that cutaneous biophysical characteristics may have a significant impact on

melasma patients.

Therefore, in this study, I measured the cutaneous biophysical characteristics of

melasma including SC hydration, sebum content, and TEWL and made comparisons between

lesional and perilesional normal skin.

- 3 -

II. MATERIALS AND METHODS

A. Subjects

A total of 16 female Korean volunteers with melasma were recruited. The mean age

was 44.2±5.36 years old (31-55 years old), and the average of disease duration was 12.9±7.2

years. All subjects have Fitzpatrick skin type III or IV. All subjects had a washout period of

at least one month from a bleaching agent or steroid containing triple agents and a washout

period of at least one year from lasers, dermabrasion, and chemical peeling. No skin care

products had been applied to the measured sites 24 hours prior to the measurements, and the

measured sites had not been washed with soaps or surfactants for at least two hours prior to

the study. A two-millimeter punch biopsy from lesional and perilesional skin of melasma was

performed in 11 of 16 volunteers. Informed written consent was obtained. This study was

approved by the institutional review board of Ajou University Hospital (IRB number:

AJIRB-MED-DEO-10-152).

- 4 -

Table 1. General characteristics of volunteers

Age Skin type Disease duration

(yrs)

Previous Medical history Skin biopsy

1 42 IV 30 None O

2 31 IV 2.3 None O

3 44 IV 5 None O

4 55 IV 20 None O

5 46 IV 23 None O

6 42 III 10 None X

7 46 III 15 None O

8 47 III 7 None X

9 51 III 18 None O

10 39 III 15 None X

11 44 III 20 None O

12 44 III 7 Anemia, Thyroid nodule X

13 43 III 10 None X

14 48 III 20 Diabetes mellitus O

15 46 IV 14 None O

16 39 III 10 None O

- 5 -

B. Measurements of biophysical characteristics

The melanin/erythema index, SC hydration capacitance, TEWL and amount of

sebum were measured on lesional and perilesional skin by respective probes (Mexameter:

MX16®; Corneometer: CM825®; Tewameter: TM210®; Sebumeter: SM810®) connected

to MPA-5® (Courage+Khazaka electronic GmbH, Köln, Germany). SC capacitance and

melanin/erythema index were measured on the right side of the face, and the final value was

expressed as the mean of three readings. TEWL was assessed on the left side of the face.

After baseline measurement of TEWL, barrier perturbation was performed by 5 times

repeated tape stripping (D-squame®) for barrier recovery rate measurement. TEWL was

measured immediately and 5 hours after tape stripping. Sebum amount was measured at 30

minutes after facial washing and at 5 hours after degreasing to evaluate sebum excretion rate.

All measurements were performed in an environmentally controlled research facility that

maintained an ambient temperature at 22-24 and relative humidity of 50℃ -55%. All

volunteers were allowed to acclimatize for 30 minutes prior to the test in order to adapt to the

room conditions.

C. Measurement of stratum corneum thickness and immunohistochemistry

Hematoxylin and eosin staining was performed using standard protocols. Under

H&E stain, digital images were captured (SPOT Flex®, SPOT Imaging Solutions, Sterling

Heights, MI, USA) for estimating the area of SC and length of SC baseline. SC thickness

was measured by the ratio of area and length of SC baseline.

In immunohistochemial analyses, formalin-fixed and paraffin-embedded tissue was

- 6 -

serial sectioned at 4.5μm and deparaffinized and rehydrated by sequential immersion in

xylene, graded concentrations of ethanol. The deparaffinized tissue sections were incubated

for 30 minutes at room temperature in a solution of 0.5% hydrogen peroxidase in methanol

to quench endogenous peroxidase activity, followed by heated for 20 minutes with citrate

buffer at pH 6.0 in a microwave or pretreated with trypsine for 10 minutes in 42 for ℃

antigen retrieval. After washing by Tris-buffered saline (TBS, 0.1mol/L, pH7.4, Dako,

Carpinteria, CA), tissue sections were incubated with primary antibodies for 30 minutes at

38 . ℃ A monoclonal antibody to peroxisome proliferator-activated receptor-α (PPAR-α;

Abcam, Cambridge, U.K.) and arachidonate 15-lipoxygenase, type B (ALOX15B, Lifespan

Biosciences, Seattle, WA, USA) were used with 1:200 and 1:100 dilution respectively. After

incubation with secondary antibody for 10 minutes, horseradish peroxidase (HRP) complex

and AEC chromogen were added for 15 minutes and 20 minutes respectively, followed by,

counterstaing was performed with hematoxylin. The image was analyzed using Image-Pro

Plus Version 4.5 (Media Cybernetics co., Silver Spring, MD, USA).

D. Statistical analysis

The SPSS 14.0 statistics program (SPSS, Inc., Chicago, IL, USA) and the GraphPad

Prism 5 software (GraphPad Software, Inc., La Jolla, CA, USA) was used for all statistical

analysis. If the data showed normality distribution, the independent t-test was used to

analyze the statistically significant difference between the melasma-involved and

perilesional normal skin; if it does not, Mann-Whitney test was used. The relationship

between each biophysical property was tested with Spearson correlation. A value of less than

- 7 -

0.05 was considered to be statistically significant. Data are expressed as mean ± standard

deviation (SD).

- 8 -

III. RESULTS

A. Melanin index and erythema index

The melanin index was significantly higher in lesional skin than in perilesional

normal skin (221.4±54.3 vs. 150.4±29.9, p<0.001; Fig 1A). The erythema index was

significantly increased in lesional skin than perilesional normal skin (323.2±60.3 vs.

272.3±34.8, p<0.012; Fig 1B). The melanin and erythema index showed a positive

correlation (Correlation coefficient: 0.703, p<0.01; Fig 1C).

A.

- 9 -

B.

C.

Fig. 1. Melanin/Erythema index; Comparison of melanin/erythema index between lesional

skin and perilesional normal skin; A. Melanin index, B. Erythema index, C. Correlation

between melanin/erythema index; Melanin index and erythema index showed positive

correlation. (*p< 0.05)

- 10 -

B. Basal stratum corneum properties

The SC hydration was significantly increased in lesional skin compared to

perilesional normal skin (66.9±9.9 vs. 58.4±10.1; p<0.029; Fig.2). However, the basal

TEWL showed no significant difference between lesional and perilesional normal skin

(15.6±4.6 vs. 13.5±4.0, p=0.210; Fig 3).

Fig. 2. Stratum corneum capacitance; Stratum corneum capacitance was significantly

higher in melasma-involved skin than perilesional normal skin. (*p< 0.05)

- 11 -

Fig. 3. Basal TEWL: There was no significant difference between lesional skin and

perilesional normal skin. (*p< 0.05)

C. Epidermal permeability barrier function

Immediately after tape stripping, the increased rate of TEWL in lesional skin was

significantly higher than that of perilesional normal skin (%, 143.2±116.4 vs. 79.5±40.9,

p=0.014; Fig 4). Furthermore, 5 hours after 5 times of tape stripping, a significant delayed

barrier recovery rate was demonstrated in lesional skin in comparison to perilesional normal

skin (%, 62.5±22.8 vs. 76.3±12.3, p=0.043; Fig 4). The melanin level was found to be

inversely correlated with TEWL levels after tape stripping (Correlation coefficient: -0.503,

p<0.05; Fig 5).

- 12 -

Fig. 4. Barrier recovery rate: Immediately after tape-stripping 5 times, the rate of TEWL in

lesional skin was significantly higher in comparison to perilesional normal skin. In addition,

5 hours after the tape stripping, the barrier recovery rate was significantly delayed in lesional

skin in comparison to perilesional normal skin. (*p< 0.05)

- 13 -

Fig. 5. Correlation between melanin index and epidermal barrier recovery rate: There

was negative correlation between the melanin index and barrier recovery rate.

D. Sebum content

Sebum amount measurement showed no significant difference between lesional

skin and perilesional normal skin at 30 minutes after facial washing (μg/cm2, 7.9±5.8 vs.

10.6±14.5, p=0.897, Fig 6). After 5 hours for acclimatization, the amount of sebum and the

sebum excretion rate during 5 hours showed no significant difference (μg/cm2, 5 hours after

degreasing: 20.5±15.4 vs. 22.4±24.1, p=0.752, Fig 6).

- 14 -

Fig. 6. Sebum contents: There were no significant differences in sebum amount at both 30

minutes and 5 hours after facial degreasing.

E. Expressions of PPAR-α and ALOX15B and SC thickness

Because lipid metabolism related genes, such as PPARA and ALOX15B were found

to be down-regulated in melasma, we examined their protein levels.(Kang et al., 2011) There

was no significant difference in immunoreactivity of PPAR-α and ALOX15B between

lesional and perilesional normal skin (Fig 7). However, we found that the SC thickness was

reduced in the lesional skin of melasma in comparison with perilesional normal skin (µm,

10.4±2.9 vs. 14.5±5.5, p=0.052, Fig 7, 8A). The SC thickness showed positive correlation

with epidermal barrier recovery rate (Correlation coefficient: 0.721, p=0.02; Fig 8B)

- 15 -

Fig. 7. Expressions of PPAR-α and ALOX15B and stratum corneum thickness: A.

Stratum corneum thickness was lower in lesional skin compared to perilesional normal skin.

B, C. There was no significant difference of PPAR-α and ALOX15B expression between

lesional and perilesional normal skin. (N: perilesional normal skin, L: Lesional skin. original

magnification x200)

- 16 -

A.

B.

Fig. 8. Stratum corneum thickness and correlation with barrier recovery rate; A. SC of

lesional skin showed reduced tendency in comparison with perilesional normal skin. B. SC

thickness showed positive correlation between epidermal barrier recovery rate.

- 17 -

IV. DISCUSSION

The present study demonstrated that melasma skin showed a normal hydration state

and sebaceous gland activity. However, the SC integrity and barrier function were impaired

in the lesional skin of melasma. The SC thickness was reduced in lesional skin, and it

correlated with the barrier recovery rate. The melanin index was also significantly related

with delayed barrier recovery.

The mechanisms underlying abnormal barrier function in melasma are unclear, but

there are possible explanations. Recently, we found the lipid metabolism-associated genes

such as peroxisome proliferator-activated receptor alpha (PPARA), arachidonate 15-

lipoxygenase, and type B (ALOX15B) were down-regulated in the lesional skin of melasma

(Kang et al., 2011). It is well known that the lipids of SC play an important role in

maintaining cutaneous barrier homeostasis. PPAR-α is an important regulator of lipid

catabolism, mediating fatty acid oxidation, fatty acid uptake, and lipoprotein assembly and

transport.(Mao-Qiang et al., 2004) Therefore, down-regulated lipid metabolism-associated

genes may be a causal factor of the impairment of epidermal barrier function in melasma,

although we could not confirm the down-regulation of these proteins by

- 18 -

immnohistochemical staining. The reduced SC thickness may play another role in barrier

impairment in lesional skin. In our study, reduced SC thickness was significantly related with

delayed barrier recovery. SC thickness is correlated linearly to the 1/TEWL value

(Weigmann et al., 2005). Furthermore, it has been reported that SC thickness is significantly

correlated with the objective score of atopic dermatitis (Nemoto-Hasebe et al., 2009). Also,

SC thickness is significantly decreased in acute eczematous atopic skin compared to non-

lesional and control healthy skin (Voegeli et al., 2009). That means that SC thickness may

influence the epidermal barrier homeostasis. Taken together, it is speculated that reduced SC

thickness and down-regulation of lipid metabolism related genes in melasma affect the

barrier function in melasma.

Chronic UV exposure may be another possible explanation for impaired barrier

function in melasma. UV exposure is a major triggering or aggravating factor for melasma

development. Indeed, previous studies have indicated that melasma lesions show a higher

degree of UV-induced damage. Increased solar elastosis in lesional skin has been shown. It

has also been shown that melasma is characterized by increased vasculature in the lesional

skin both clinically and histologically (Voegeli et al., 2009). Expression of VEGF, a major

- 19 -

angiogenic factor of UV irradiated skin, is upregulated in melasma lesions compared to

perilesional normal skin. In literature, chronic UV exposure influences cutaneous fatty acid

metabolism and barrier function (Merle et al., 2010). Also, chronic UV irradiation reduces

the epidermal free fatty acid and triglyceride synthesis that has an important role in

epidermal barrier homeostasis (Kim et al., 2010). In addition, UVB exposure is detrimental

to the epidermal permeability barrier in a dose- and time- dependent manner (Haratake et al.,

1997). In photo-aged skin, barrier recovery is known to be significantly delayed (Reed et al.,

1997). Therefore, an altered barrier function in melasma might be a result of the chronic UV

exposure and accompanying epidermal hyperpigmentation. Interestingly, we found a

negative correlation between melanin index and barrier recovery rate. It means that patients

with severe melasma may have poor SC.

Very recently, it has been suggested that barrier function is influenced by

pigmentation in the SC (Elias et al., 2009). Gunathilake et al. (Gunathilake et al., 2009)

reported that skin type IV-V subjects have more acidic SC due to more melanosomes than

pale-skinned subjects, and these acidic conditions were attributed to enhanced SC integrity

and accelerated barrier recovery in darker skins (Bhatnagar et al., 1993; Puri et al., 2000).

- 20 -

Unfortunately, we did not measure the skin surface pH but the present study does not reveal

a positive relationship between melanin index and barrier recovery rate. Rather, there was a

negative correlation. These difference might be explained by the fact that molecules of

melanin in melasma are different from normal melanin (Moncada et al., 2009). Especially,

Raman skin spectroscopy measurements showed that melasma patients have degraded

melanin in the SC of lesional skin. Of course, there are inter-individual differences in

subjects’ race and geographic location.

The present study also demonstrated a significant increase of both the melanin and

erythema index in melasma-involved skin. Also, a positive correlation appeared between the

melanin index and the erythema index. The increased melanin index was reflected as the

hallmark of melasma in histological studies such as epidermal hyperpigmentation (Kang et

al., 2002). Furthermore, the increased erythema index in melasma-involved skin

corresponded with the results of earlier studies, which reported that melasma patients

showed higher erythema intensity and increased vascularity in the melasma lesions than that

of perilesional normal skin (Kim et al., 2007). In a histopathologic study, the number of

dermal vessels had a positive relationship with pigmentation in lesional skin (Kim et al.,

- 21 -

2007). These results have suggested that the connection between vessels and cutaneous

pigmentation. It should be further studied on a large scale in the future.

- 22 -

V. CONCLUSION

In conclusion, in the present study, I have demonstrated that the melanin index,

erythema index and SC hydration were significantly higher in lesional skin compared to

perilesional normal skin. However, the basal TEWL and sebum excretion rate showed no

significant difference. Interestingly, the epidermal barrier recovery in lesional skin is delayed,

and SC integrity is decreased in lesional skin compared to perilesional normal skin. The

melanin index showed to be inversely correlated with the barrier recovery rate. In

histopathologically, SC thickness in lesional skin decreased than perilesional normal skin

and correlated with the barrier recovery rate. These findings suggested that melasma skin

have a normal hydration state and sebaceous gland activity, whereas the SC integrity and

barrier function were impaired in melasma skin. Decreased SC integrity is one of major

biophysical characteristic of melasma.

- 23 -

REFERENCES

1. Berardesca E, Maibach H: Racial differences in skin pathophysiology. J Am Acad

Dermatol 34: 667-672, 1996

2. Bhatnagar V, Anjaiah S, Puri N, Darshanam BN, Ramaiah A: pH of melanosomes of

B 16 murine melanoma is acidic: its physiological importance in the regulation of

melanin biosynthesis. Arch Biochem Biophys 307: 183-192, 1993

3. Elias PM, Menon G, Wetzel BK, Williams JJ: Evidence that stress to the epidermal

barrier influenced the development of pigmentation in humans. Pigment Cell

Melanoma Res 22: 420-434, 2009

4. Gunathilake R, Schurer NY, Shoo BA, Celli A, Hachem JP, Crumrine D, Sirimanna

G, Feingold KR, Mauro TM, Elias PM: pH-regulated mechanisms account for

pigment-type differences in epidermal barrier function. J Invest Dermatol 129: 1719-

1729, 2009

5. Haratake A, Uchida Y, Schmuth M, Tanno O, Yasuda R, Epstein JH, Elias PM,

Holleran WM: UVB-induced alterations in permeability barrier function: roles for

epidermal hyperproliferation and thymocyte-mediated response. J Invest Dermatol

108: 769-775, 1997

6. Hernandez-Barrera R, Torres-Alvarez B, Castanedo-Cazares JP, Oros-Ovalle C,

Moncada B: Solar elastosis and presence of mast cells as key features in the

pathogenesis of melasma. Clin Exp Dermatol 33: 305-308, 2008

- 24 -

7. Kang HY, Suzuki I, Lee DJ, Ha J, Reiniche P, Aubert J, Deret S, Zugaj D, Voegel JJ,

Ortonne J-P: Transcriptional profiling shows altered expression of Wnt pathway-

and lipid metabolism-related genes as well as melanogenesis-related genes in

melasma. J Invest Dermatol in press, 2011

8. Kang WH, Yoon KH, Lee ES, Kim J, Lee KB, Yim H, Sohn S, Im S: Melasma:

histopathological characteristics in 56 Korean patients. Br J Dermatol 146: 228-237,

2002

9. Kim EH, Kim YC, Lee ES, Kang HY: The vascular characteristics of melasma. J

Dermatol Sci 46: 111-116, 2007

10. Kim EJ, Jin XJ, Kim YK, Oh IK, Kim JE, Park CH, Chung JH: UV decreases the

synthesis of free fatty acids and triglycerides in the epidermis of human skin in vivo,

contributing to development of skin photoaging. J Dermatol Sci 57: 19-26, 2010

11. Kompaore F, Marty JP, Dupont C: In vivo evaluation of the stratum corneum barrier

function in blacks, Caucasians and Asians with two noninvasive methods. Skin

Pharmacol 6: 200-207, 1993

12. Mao-Qiang M, Fowler AJ, Schmuth M, Lau P, Chang S, Brown BE, Moser AH,

Michalik L, Desvergne B, Wahli W, Li M, Metzger D, Chambon PH, Elias PM,

Feingold KR: Peroxisome-proliferator-activated receptor (PPAR)-gamma activation

stimulates keratinocyte differentiation. J Invest Dermatol 123: 305-312, 2004

13. Merle C, Laugel C, Baillet-Guffroy A: Effect of UVA or UVB irradiation on

cutaneous lipids in films or in solution. Photochem Photobiol 86: 553-562, 2010

- 25 -

14. Moncada B, Sahagun-Sanchez LK, Torres-Alvarez B, Castanedo-Cazares JP,

Martinez-Ramirez JD, Gonzalez FJ: Molecular structure and concentration of

melanin in the stratum corneum of patients with melasma. Photodermatol

Photoimmunol Photomed 25: 159-160, 2009

15. Nemoto-Hasebe I, Akiyama M, Nomura T, Sandilands A, McLean WH, Shimizu H:

Clinical severity correlates with impaired barrier in filaggrin-related eczema. J Invest

Dermatol 129: 682-689, 2009

16. Puri N, Gardner JM, Brilliant MH: Aberrant pH of melanosomes in pink-eyed

dilution (p) mutant melanocytes. J Invest Dermatol 115: 607-613, 2000

17. Reed JT, Elias PM, Ghadially R: Integrity and permeability barrier function of

photoaged human epidermis. Arch Dermatol 133: 395-396, 1997

18. Reed JT, Ghadially R, Elias PM: Skin type, but neither race nor gender, influence

epidermal permeability barrier function. Arch Dermatol 131: 1134-1138, 1995

19. Voegeli R, Rawlings AV, Breternitz M, Doppler S, Schreier T, Fluhr JW: Increased

stratum corneum serine protease activity in acute eczematous atopic skin. Br J

Dermatol 161: 70-77, 2009

20. Weigmann HJ, Ulrich J, Schanzer S, Jacobi U, Schaefer H, Sterry W, Lademann J:

Comparison of transepidermal water loss and spectroscopic absorbance to quantify

changes of the stratum corneum after tape stripping. Skin Pharmacol Physiol 18:

180-185, 2005

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- 국 요약 -

미 피부 생 리학 특

아주 학 학원 학과

이 동

(지도 : 강 희 )

연구 경: 미는 피부 피 색소 증가 손상 피부를 특징 하는

질 이다. 이런 미 조직학 특징 미 자에 있어 피부 리학

특 변 를 야 시켰 것 생각 다.

연구목 : 따라 본 연구에 는 미 병변에 피부 리학 특 인

상 피부 하여 살펴보았다.

연구 법: 16 명 미 자를 모집하여 라닌 지 , 지 , 피 분량,

피지량, 경 피 분 손실량 미 피부 병변과 인 상 피부에 하 다.

경 피 분 손실량 경우 5 회 이프 스트리핑 법 피부 장벽에 손상

가한 직후 5 시간 동안 피부 안 취한 후 재 하여 각질 안

피부 장벽 회복 속도를 하 다. 피지량 경우 얼굴 가볍게 한

이후 각각 30 분, 5 시간 동안 피부 안 취한 후 하 다. 11 명

자에 는 2mm punch 를 이용하여 병변 인 상 피부에 피부 조직

검사를 시행하여 각질 게 지질 사 자인 peroxisome

- 27 -

proliferator-activated receptor alpha (PPAR-α), and arachidonate 15-lipoxygenase, type B

(ALOX15B) 면역조직 학염색 시행하 다.

연구결과: 라닌 지 , 지 피부 분량 인 피부에 해 미

병변에 통계 하게 증가한 면 초 경 피 분 손실량 미

상 피부 사이에 통계 한 차이는 보이지 않았다. 하지만 이프 스트리핑

법 피부 장벽에 손상 가한 직후에 한 경 피 분 손실량

증가 미 병변에 인 상 피부에 피해 통계 하게 증가 어

있었 며 5 시간 후 한 피부 장벽 회복 미 병변이 인 상 피부에

해 통계 하게 감소하는 양상 찰 었다. 또한 라닌 지 피부 장벽

회복 속도간에 상 계가 있는 것 나타났다. 미 병변과 인 상

피부 사이에 피지량 통계 한 차이를 보이지 않았다. 피부 조직에

PPAR-α ALOX15B 미 상 피부 사이에 차이를 보이지

않았 나 각질 께는 미 병변에 감소 는 양상 찰 었다. 또한 이

각질 께는 장벽 회복 속도 양 상 계가 있었다.

결 : 미 병변 상 인 분 함 량과 피지 분 를 보 다. 하지만

각질 안 장벽 능 미 병변이 인 상 피부에 해 손상 어

있 인할 있었다. 각질 께는 미 병변에 감소 어 있었 며

이는 피부 장벽 회복 속도 양 상 계가 있었다. 따라 이 연구는 피부

장벽 능 회복 또한 미 료에 있어 고 해야 한다는 것 시하는

결과라 할 있다.

핵심어: 미, 각질 , 피부 장벽 능, 경 피 분 손실량