스트론튬 이온이 무모 생쥐의 표피 투과 장벽 회복에 미치는 영향

김현정 ( Hyun Jeong Kim ),김민정 ( Min Jung Kim ),정세규 ( Se Kyoo Jeong ),최기주 ( Ki Ju Choi ),서정택 ( Jeong Taek Seo ),최응호 ( Eung Ho Choi ),안성구 ( Sung Ku Ahn ),이승헌 ( Sung Hun Lee ) 대한피부과학회 2006 대한피부과학회지 Vol.44 No.11

Background: Several ions, such as calcium or magnesium ions, are reported to have regulatory effects on epidermal permeability barrier homeostasis. Recently, it has been suggested that strontium ion can play a substitutive role for calcium ion in various cellular reactions. Objective: This study was conducted to investigate the effects of strontium ion, either alone or in combination with calcium or magnesium ions, on epidermal permeability barrier homeostasis. Methods: Female hairless mice were used to study the effects of various ions on epidermal permeability barrier recovery. Calcium chloride solution, magnesium chloride solution or strontium chloride solution were topically applied to barrier-disrupted skin, either alone or simultaneously. Change of transepidermal water loss, which represents permeability barrier function, was measured by TEWameter and morphological change was also observed by light and electron microscopy. Results: Topical application of strontium chloride solution accelerated permeability barrier recovery rate, compared with vehicle-applied skin. Magnesium chloride solution also accelerated barrier recovery rate, as reported in previous studies. Interestingly, simultaneous application of strontium and calcium ions significantly accelerated barrier recovery rate, compared to application of strontium or calcium ion alone. Nile red staining confirmed the increased neutral lipid deposition in strontium ion applied skin. Electron microscopic observation also revealed an increased lamellar body secretion in strontium ion applied skin. Conclusion: Strontium ion can play a regulatory role in epidermal permeability barrier homeostasis due to, at least in part, its competitive action on calcium ion for the same ion channel. (Korean J Dermatol 2006;44(11):1309~1316)

Basic Concept of Epidermal Barrier

이해진 ( Hae-jin Lee ) 한국피부장벽학회 2016 한국피부장벽학회지 Vol.18 No.1

The skin, as an interface between the organism and the external environment, plays a major role in protecting and supporting the life it encloses. Elias proposed the `brick and mortar model`, in which the SC is composed of flat cells of corneocytes with cornified envelope and cytoskeletal elements, as well as corneodesmosomes (bricks) surrounded by lipid-enriched intercellular domains matrix (mortar). Since then, many studies have been performed to elucidate the role of the SC at the organismal, biochemical and molecular biological levels. During epidermal differentiation, lipids are synthesized in the keratinocytes and extruded into the extracellular domains, where they form extracellular lipid-enriched layers. Meanwhile, Human epidermis displays a characteristic calcium gradient, with lower calcium levels in the basal and spinous layers, which increases progressively towards the outer SG. The Ca2+ gradient has been shown to regulate lamellar body secretion independent of barrier formation. Changes in epidermal differentiation and lipid composition lead to a disturbed skin barrier as well as loss of calcium gradient, which is important for the pathogenesis of atopic dermatitis, psoriasis, ichthyosis and contact dermatitis. In this review, we discuss the basic concept and components of epidermal barrier.

Basic Concept and Components of Skin Barrier

( Seung Phil Hong ) 한국피부장벽학회 2011 한국피부장벽학회지 Vol.13 No.1

The skin forms an effective barrier between the organism and the environment preventing invasion of pathogens and fending off chemical and physical assaults, as well as the unregulated loss of water and solutes within our body. Two compartment model, also called as ``bricks and mortar model`` has been the best explanation for the structure of epidermal permeability barrier. It consists of protein-enriched cells as bricks (corneocytes with cornified envelope and cytoskeletal elements, as well as corneodesmosomes) and lipid-enriched intercellular domains as mortar. During epidermal differentiation lipids are synthesized in the keratinocytes and extruded into the extracellular domains, where they form extracellular lipid-enriched layers. The lipids that constitute the extracellular matrix have a unique composition and are 50% ceramides, 25% cholesterol, and 15% free fatty acids. The cornified cell envelope, a tough protein-lipid polymer structure, resides below the cytoplasmic membrane on the exterior of the corneocytes. Ceramides are covalently bound to cornified envelope proteins and form the backbone for the subsequent addition of free ceramides, free fatty acids and cholesterol in the stratum corneum. Changes in epidermal differentiation and lipid composition lead to a disturbed skin barrier, which is important for the pathogenesis of contact dermatitis, ichthyosis, psoriasis and atopic dermatitis. This review introduces an overview of major components of the skin barrier, explaining how barrier function is regulated.

Basic Concept of Epidermal Barrier

( Hae-jin Lee ) 한국피부장벽학회 2016 한국피부장벽학회지 Vol.18 No.1

The skin, as an interface between the organism and the external environment, plays a major role in protecting and supporting the life it encloses. Elias proposed the `brick and mortar model`, in which the SC is composed of flat cells of corneocytes with cornified envelope and cytoskeletal elements, as well as corneodesmosomes (bricks) surrounded by lipid-enriched intercellular domains matrix (mortar). Since then, many studies have been performed to elucidate the role of the SC at the organismal, biochemical and molecular biological levels. During epidermal differentiation, lipids are synthesized in the keratinocytes and extruded into the extracellular domains, where they form extracellular lipid-enriched layers. Meanwhile, Human epidermis displays a characteristic calcium gradient, with lower calcium levels in the basal and spinous layers, which increases progressively towards the outer SG. The Ca2+ gradient has been shown to regulate lamellar body secretion independent of barrier formation. Changes in epidermal differentiation and lipid composition lead to a disturbed skin barrier as well as loss of calcium gradient, which is important for the pathogenesis of atopic dermatitis, psoriasis, ichthyosis and contact dermatitis. In this review, we discuss the basic concept and components of epidermal barrier.

Role of Ceramide and Its Metabolites in the Regulation of Epidermal Barrier Function

( Sekyoo Jeong ),( Kyong-oh Shin ),( Kyungho Park ) 한국피부장벽학회 2018 한국피부장벽학회지 Vol.20 No.1

Ceramide is a main epidermal lipid and is composed of long-chain aminoalcohol and amide-linked fatty acids, whose chain lengths are 16-20 and 16-36, respectively. Emerging evidences demonstrated that ceramide plays a primary structural role in forming epidermal permeability barrier. In addition, ceramide and its metabolites, including sphingosine-1-phosphate, serve as signaling lipid to modulate multiple cellular functions, e.g., proliferation, differentiation, and apoptosis, as well as epidermal antimicrobial barrier. Here, we describe the signaling roles and current knowledge of ceramide and its metabolites in the regulation of epidermal barrier function.

장시간 수화가 표피투과장벽에 미치는 영향

안성구 ( Sung Ku Ahn ),이은희 ( Eun Hee Lee ),홍승필 ( Seung Phil Hong ),최응호 ( Eung Ho Choi ),이승헌 ( Seung Hun Lee ) 대한피부과학회 2007 大韓皮膚科學會誌 Vol.45 No.1

Background: Water exposure is considered an important causative factor of irritant contact dermatitis. It is also known that water exposure can disrupt the stratum corneum (SC). However, there are only a few morphologic studies on the effect of water contact on the skin. Objective: The aim of our study was to investigate the effects of prolonged water exposure on the permeability barrier and the ultrastructure of the SC intercellular lipids. Methods: After prolonged water exposure of hairless mouse skin in vivo for 24, 36, 48, and 72 hrs respectively, the permeability barrier function was assessed by transepidermal water loss (TEWL) measurement, and the ultrastructure of SC by electron microscopy using osmium tetraoxide and ruthenium tetraoxide postfixation and calcium ion capture cytochemistry. Additionally, the lipid composition was evaluated using confocal microscopy with nile red stain and the integrity of the SC assessed using a lanthanum tracer. Results: After prolonged water exposure, water caused a significant increase in TEWL with disappearance of the calcium gradient, but this did not significantly influence the recovery rate of TEWL. The intercellular lipids were disrupted, and multiple lacunae containing abnormal delaminated materials within the intercellular spaces were observed. Lanthanum tracer penetrated into the intercellular space of the SC. There was a progressive decrease in nile red staining with neutral lipid content. With increasing exposure to water, these results were more evident. Conclusion: Our results provide a better understanding of the disruptive effect of prolonged water exposure on barrier lipids, the penetration-enhancing effect of water and the increased susceptibility to irritants, with regard to duration of water exposure. (Korean J Dermatol 2007;45(1):23~33)

표피장벽 손상 후 회복에 대한 이온영동 효과

이승헌 ( Seung Hun Lee ),강소군 ( Shaojun Jiang ),박태현 ( Tae Hyun Park ),최승호 ( Choong Bae Yoo ),안성구 ( Eung Ho Choi ),유총배 ( Sung Ku Ahn ) 대한피부과학회 1996 대한피부과학회지 Vol.34 No.3

Background: The stratum corneum(SC) has a permeability barrier function which regulates percutaneous absorption by the inhibition of transepidermal water loss(TEWL). Acute mechanical or chemical disruption of the SC induces the impairment of the permeability barrier and so increases the TEWL. The calciumtion has been recognized as an important ion in the recovery of the skin barrier. Recently the main delivery pathway of iontophoretic drugs have been suggested by SC interstices. However the morphologic changes in the SC interstices and calcium after iontophoresis have not been reported. Objective : The aim of our study is to confirm that iontophoresis may induce changes in the SC interstices and delay the recovery of the barrier after disruption. Material and Methods : After tape stripping the hairless mouse flank skin, the iontophoresis power supply (6V, 0.6mA) was connected to the patch atiached for 2.5 hours to the stripped site. We checked the THWL 0, 2.5, 6, 12, 18, 24 hours after the tape stripping and obtained specimens and performed osmium tetroxide, ruthenium tetroxide postfixation and calcium ion-capture cytochemical stains for electron microscopic study. Results : The recovery rate of the TEWL in iontophoresis was lower than in the control. This was especially so in the anouse which had received anode iontophoresis for 6 hours. It showed statistically lower TEWL than in the control(p<0.05). Anode iontophoresis induced low calcium in stratum granulosum (SG), but cathode iontophoresis induced high calcium in SC. After iontophoresis there were changes in the SC interstices structures. Conclusion : Iontophoresis can induce changes in the SC interstices and calcium distribution and so may help the topical drug delivery system. (Kor J Dermatol 1996;34(3): 375-380)

테스토스테론이 피부장벽에 미치는 효과

박하나 ( Ha Na Bak ),최응호 ( Eung Ho Choi ),이광길 ( Kwang Gil Lee ),홍승필 ( Seung Phil Hong ),이승헌 ( Seung Hun Lee ),안성구 ( Sung Ku Ahn ) 대한피부과학회 2005 대한피부과학회지 Vol.43 No.2

침수(浸水)가 급성 피부장벽손상 후 장벽회복에 미치는 영향

김도원,이성훈,전재복,정상립 경북대학교 의학연구소 2000 경북대학교병원의학연구소논문집 Vol.4 No.1

Background : If the skin is kept in continuous contact with water or other solutions after acute barrier perturbation, the pattern of barrier recovers will be different from that of the air exposure state at room temperature. Changes in the concentration of the solution also make a difference in the pattern of barrier recovery. However, there have been only a few studies on the difference of the barrier recovery or the changes in stratum corneum lipid between cases in the water immersion state and the air exposure state. Objective : We studied the effect of immersion on the recovery of the epidermal barrier after acute perturbation so as to give aid to the basic research of the epidermal barrier and clinical application in prevention and treatment of contact dermatitis, hand eczema, and other occupational dermatoses. Methods : After disruption of the epidermal barrier by tape stripping, hairless mice were immersed in temperature regulated hypotonic, isotonic, or hypertonic solutions, respectively. The pattern of barrier recovery with time was evaluated and compared with that of the air exposure group by means of TEWL measurement, and histochemical stain with Nile red. Results : Immersion intro water or solution without time to recovery after epidermal barrier disruption makes the recovery rate slower than that of the air exposure group except for the isotonic solution immersing group. Conclusion : For the normal recovery or prevention of the deterioration of the epidermal barrier, we should keep in mind to avoid the exposure to water or others solutions when acute or chronic barrier perturbation has developed. In addition, it would be better to use normal saline or other isotonic solutions, which do not disturb the normal barrier recovery Process, to decrease damage to the epidermal barrier when it cannot help immersing into the solution. (Korean J Dermatol 1999;37(10) 1435∼1441)

The effect of two Terpenoids, Ursolic acid and Oleanolic acid on epidermal permeability barrier and simultaneously on dermal functions

( Suk Won Lim ),( Sung Won Jung ),( Sung Ku Ahn ),( Bora Kim ),( Hee Chang Ryoo ),( Seung Hun Lee ) 대한화장품학회 2003 대한화장품학회지 Vol.29 No.2

Ursolic acid (UA) and Oleanolic acid (ONA), known as urson, micromeroJ and malol, are pentacyclic triterpenoid compounds which naturally occur in a large number of vegetarian foods, medicinal herbs, and plants. They may occur in their free acid form or as aglycones for triterpenoid saponins, which are comprised of a triterpenoid aglycone, linked to one or more sugar moieties. Therefore UA and ONA are similar in pharmacological activity. Lately scientific research, which led to the identification of UA and ONA, revealed that several pharmacological effects, such as antitumor, hepato-protective, anti-inflammatory, anticarcinogenic, antimicrobial, and anti-hyperlipidemic could be attributed to UA and ONA. Here, we introduced the effect of UA and ONA on acutely barrier disrupted and normal hairless mouse skin. To evaluate the effects of UA and ONA on epidermal permeability barrier recovery, both flanks of 8-12 week-old hairless mice were topically treated with either 0.01-0.1 mg/ml UA or 0.1-1 mg/ml ONA after tape stripping, and TEWL (Transepidermal water loss) was measured. The recovery rate increased in those UA or ONA treated groups (0.1 mg/ml UA and 0.5 mg/ml ONA) at 6 h more than 20% compared to vehicle treated group (p<0.05). Here, we introduced the effects of UA and ONA on acute barrier disruption and normal epidermal permeability barrier function. For verifying the effects of UA and ONA on normal epidermal barrier, hydration and TEWL were measured for 1 and 3 weeks after UA and ONA applications (2mg/ml per day). We also investigated the features of epidermis and dermis using electron microscopy (EM) and light microscopy (LM). Both samples increased hydration compared to vehicle group from 1 week without TEWL alteration (p< O.005). EM examination using Ru04 and Os04 fixation revealed that secretion and numbers of lamellar bodies and complete formation of lipid bilayers were most prominent (ONA ≥ UA >Vehicle). LM finding showed that thickness of stratum corneum (SC) was slightly increased and especially epidermal thickening and flattening was observed (UA>ONA>Veh). We also observed that UA and ONA stimulate epidermal keratinocyte differentiation via PPAR a. Protein expression of involucrin, loricrin, and filaggrin increased at least 2 and 3 fold in HaCaT cells treated with either ONA (10 μM) or UA (10 μM) for 24h respectively. This result suggested that the UA and ONA can improve epidermal permeability barrier function and induce the epidermal keratinocyte differentiation via PPAR a. Using Masson-trichrome and elastic fiber staining, we observed collagen thickening and elastic fiber elongation by UA and ONA treatments. In vitro results of collagen and elastin synthesis and elastase inhibitory activity measurements were also confirmed in vivo findings. These data suggested that the effects of UA and ONA related to not only epidermal permeability barrier functions but also dermal collagen and elastic fiber synthesis. Taken together, UA and ONA can be relevant candidates to improve epidermal and dermal functions and pertinent agents for cosmeseutical applications.