Dermal Fibroblast CCN1 Expression in Mice Recapitulates Human Skin Dermal Aging.



Quan, Taihao, Xiang, Yaping, Liu, Yingchun, Qin, Zhaoping, Yang, Yan, Bou-Gharios, George ORCID: 0000-0002-9563-9418, Voorhees, John J, Dlugosz, Andrzej A and Fisher, Gary J
(2020) Dermal Fibroblast CCN1 Expression in Mice Recapitulates Human Skin Dermal Aging. The Journal of investigative dermatology.

WarningThere is a more recent version of this item available.
[img] Text
2019_11_14_CCN1 Manuscript v2.docx - Submitted Version

Download (112kB)

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 (ECM) associated matricellular protein, is elevated in dermal fibroblasts in aged human skin. Towards constructing a mouse model to study 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 TGF-β signaling and increased expression of matrix metalloproteinases, driven up induction of c-Jun/AP-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 mechanisms of skin aging and age-related skin disorders.

Item Type: Article
Depositing User: Symplectic Admin
Date Deposited: 01 Sep 2020 08:17
Last Modified: 03 Sep 2020 10:09
DOI: 10.1016/j.jid.2020.07.019
URI: http://livrepository.liverpool.ac.uk/id/eprint/3099109

Available Versions of this Item