Dermal Fibroblast CCN1 Expression in Mice Recapitulates Human Skin Dermal Aging

Quan, Taihao, Xiang, Yaping, Liu, Yingchun, Qin, Zhaoping, Yang, Yan, Bou-Gharios, George, Voorhees, John J, Dlugosz, Andrzej A and Fisher, Gary J (2021) Dermal Fibroblast CCN1 Expression in Mice Recapitulates Human Skin Dermal Aging. JOURNAL OF INVESTIGATIVE DERMATOLOGY, 141 (4). pp. 1007-1016.

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Official URL: http://dx.doi.org/10.1016/j.jid.2020.07.019

Abstract

The aging process deleteriously alters the structure and function of dermal collagen. These alterations result in thinning, fragility, wrinkles, laxity, impaired wound healing, and a microenvironment conducive to cancer. However, the key factors responsible for these changes have not been fully elucidated, and relevant models for the study of skin aging progression are lacking. CCN1, a secreted extracellular matrix‒associated matricellular protein, is elevated in dermal fibroblasts in aged human skin. Toward constructing a mouse model to study the key factors involved in skin-aging progression, we demonstrate that transgenic mice, with selective expression of CCN1 in dermal fibroblasts (COL1A2-CCN1), display accelerated skin dermal aging. The aged phenotype in COL1A2-CCN1 mice resembles aged human dermis: the skin is wrinkled and the dermis is thin and composed of loose, disorganized, and fragmented collagen fibrils. These dermal alterations reflect reduced production of collagen due to impaired TGFβ signaling and increased expression of matrix metalloproteinases driving the induction of c-Jun/activator protein-1. Importantly, similar mechanisms drive human dermal aging. Taken together, the data demonstrate that elevated expression of CCN1 by dermal fibroblasts functions as a key mediator of dermal aging. The COL1A2-CCN1 mouse model provides a novel tool for understanding and studying the mechanisms of skin aging and age-related skin disorders.

Item Type:	Article
Uncontrolled Keywords:	Cells, Cultured, Fibroblasts, Dermis, Animals, Mice, Transgenic, Humans, Mice, Collagen, Collagen Type I, Models, Animal, Up-Regulation, Skin Aging, Promoter Regions, Genetic, Cysteine-Rich Protein 61, HEK293 Cells, Primary Cell Culture
Depositing User:	Symplectic Admin
Date Deposited:	03 Sep 2020 10:09
Last Modified:	16 Oct 2023 22:46
DOI:	10.1016/j.jid.2020.07.019
Related URLs:	Author Publisher
URI:	https://livrepository.liverpool.ac.uk/id/eprint/3099715