The Human Epidermal Basement Membrane: A Shaped and Cell Instructive Platform That Aging Slowly Alters

Overview

Journal Biomolecules

Publisher MDPI

Specialties Biochemistry
Molecular Biology

Date 2020 Dec 2

PMID 33260936

Citations 43

Authors

Eva Roig-Rosello

Patricia Rousselle

Affiliations

Soon will be listed here.

Abstract

One of the most important functions of skin is to act as a protective barrier. To fulfill this role, the structural integrity of the skin depends on the dermal-epidermal junction-a complex network of extracellular matrix macromolecules that connect the outer epidermal layer to the underlying dermis. This junction provides both a structural support to keratinocytes and a specific niche that mediates signals influencing their behavior. It displays a distinctive microarchitecture characterized by an undulating pattern, strengthening dermal-epidermal connectivity and crosstalk. The optimal stiffness arising from the overall molecular organization, together with characteristic anchoring complexes, keeps the dermis and epidermis layers extremely well connected and capable of proper epidermal renewal and regeneration. Due to intrinsic and extrinsic factors, a large number of structural and biological changes accompany skin aging. These changes progressively weaken the dermal-epidermal junction substructure and affect its functions, contributing to the gradual decline in overall skin physiology. Most changes involve reduced turnover or altered enzymatic or non-enzymatic post-translational modifications, compromising the mechanical properties of matrix components and cells. This review combines recent and older data on organization of the dermal-epidermal junction, its mechanical properties and role in mechanotransduction, its involvement in regeneration, and its fate during the aging process.

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References

Ghosh K, Capell B . The Senescence-Associated Secretory Phenotype: Critical Effector in Skin Cancer and Aging. J Invest Dermatol. 2016; 136(11):2133-2139. PMC: 5526201. DOI: 10.1016/j.jid.2016.06.621. View

McGrath J . Recently Identified Forms of Epidermolysis Bullosa. Ann Dermatol. 2016; 27(6):658-66. PMC: 4695416. DOI: 10.5021/ad.2015.27.6.658. View

Sher I, Zisman-Rozen S, Eliahu L, Whitelock J, Maas-Szabowski N, Yamada Y . Targeting perlecan in human keratinocytes reveals novel roles for perlecan in epidermal formation. J Biol Chem. 2005; 281(8):5178-87. DOI: 10.1074/jbc.M509500200. View

Discher D, Janmey P, Wang Y . Tissue cells feel and respond to the stiffness of their substrate. Science. 2005; 310(5751):1139-43. DOI: 10.1126/science.1116995. View

Watt F, Jordan P, ONeill C . Cell shape controls terminal differentiation of human epidermal keratinocytes. Proc Natl Acad Sci U S A. 1988; 85(15):5576-80. PMC: 281801. DOI: 10.1073/pnas.85.15.5576. View

Lawlor K, Kaur P . Dermal Contributions to Human Interfollicular Epidermal Architecture and Self-Renewal. Int J Mol Sci. 2015; 16(12):28098-107. PMC: 4691026. DOI: 10.3390/ijms161226078. View

Nagaraju G, Dontula R, El-Rayes B, Lakka S . Molecular mechanisms underlying the divergent roles of SPARC in human carcinogenesis. Carcinogenesis. 2014; 35(5):967-73. DOI: 10.1093/carcin/bgu072. View

Elamaa H, Sormunen R, Rehn M, Soininen R, Pihlajaniemi T . Endostatin overexpression specifically in the lens and skin leads to cataract and ultrastructural alterations in basement membranes. Am J Pathol. 2005; 166(1):221-9. PMC: 1602290. DOI: 10.1016/S0002-9440(10)62246-8. View

Li S, Edgar D, Fassler R, Wadsworth W, Yurchenco P . The role of laminin in embryonic cell polarization and tissue organization. Dev Cell. 2003; 4(5):613-24. DOI: 10.1016/s1534-5807(03)00128-x. View

10.

Ya C, Carranca M, Sigaudo-Roussel D, Faure P, Fromy B, Debret R . Substrate softness promotes terminal differentiation of human keratinocytes without altering their ability to proliferate back into a rigid environment. Arch Dermatol Res. 2019; 311(10):741-751. DOI: 10.1007/s00403-019-01962-5. View

11.

Oguchi M, Kobayasi T, ASBOE-HANSEN G . Secretion of type IV collagen by keratinocytes of human adult. J Invest Dermatol. 1985; 85(1):79-81. DOI: 10.1111/1523-1747.ep12275360. View

12.

Olenius M, Dalsgaard C, Wickman M . Mitotic activity in expanded human skin. Plast Reconstr Surg. 1993; 91(2):213-6. DOI: 10.1097/00006534-199302000-00001. View

13.

Franzke C, Tasanen K, Schumann H, Bruckner-Tuderman L . Collagenous transmembrane proteins: collagen XVII as a prototype. Matrix Biol. 2003; 22(4):299-309. DOI: 10.1016/s0945-053x(03)00051-9. View

14.

Rousselle P, Montmasson M, Garnier C . Extracellular matrix contribution to skin wound re-epithelialization. Matrix Biol. 2018; 75-76:12-26. DOI: 10.1016/j.matbio.2018.01.002. View

15.

Longmate W, Monichan R, Chu M, Tsuda T, Mahoney M, DiPersio C . Reduced fibulin-2 contributes to loss of basement membrane integrity and skin blistering in mice lacking integrin α3β1 in the epidermis. J Invest Dermatol. 2014; 134(6):1609-1617. PMC: 4020984. DOI: 10.1038/jid.2014.10. View

16.

Atiyeh B, Costagliola M . Cultured epithelial autograft (CEA) in burn treatment: three decades later. Burns. 2007; 33(4):405-13. DOI: 10.1016/j.burns.2006.11.002. View

17.

Downing B, Cornwell K, Toner M, Pins G . The influence of microtextured basal lamina analog topography on keratinocyte function and epidermal organization. J Biomed Mater Res A. 2004; 72(1):47-56. DOI: 10.1002/jbm.a.30210. View

18.

Kobiela T, Lelen-Kaminska K, Stepulak M, Lekka M, Malejczyk M, Arct J . The influence of surfactants and hydrolyzed proteins on keratinocytes viability and elasticity. Skin Res Technol. 2012; 19(1):e200-8. DOI: 10.1111/j.1600-0846.2012.00628.x. View

19.

Crest J, Diz-Munoz A, Chen D, Fletcher D, Bilder D . Organ sculpting by patterned extracellular matrix stiffness. Elife. 2017; 6. PMC: 5503509. DOI: 10.7554/eLife.24958. View

20.

Giangreco A, Goldie S, Failla V, Saintigny G, Watt F . Human skin aging is associated with reduced expression of the stem cell markers beta1 integrin and MCSP. J Invest Dermatol. 2009; 130(2):604-8. DOI: 10.1038/jid.2009.297. View