Cellular retinoic acid binding protein-II expression and its potential role in skin aging.

Alessandra Bielli,Elena Campione,Sara Agostinelli,Federico D’Amico,Augusto Orlandi,Chiara Tarquini,Gaetana Costanza,Maria Giovanna Scioli,Filadelfo Coniglione,Elena Doldo,Daniela Passeri

doi:10.18632/aging.101813

Abstract

Skin aging is an intricate biological process consisting of intrinsic and extrinsic alterations of epidermal and dermal structures. Retinoids play an important role in epidermal cell growth and differentiation and are beneficial to counteract skin aging. Cellular retinoic acid binding protein-II (CRABP-II) selectively binds all trans-retinoic acid, the most active retinoid metabolite, contributing to regulate intracytoplasmic retinoid trafficking and keratinocyte differentiation. Immunohistochemistry revealed a reduced epidermal and dermal CRABP-II expression in aged human and mouse skin. To better clarify the role of CRABP-II, we investigated age-related skin changes in CRABP-II knock-out mice. We documented an early reduction of keratinocyte layers, proliferation and differentiation rate, dermal and hypodermal thickness, pilosebaceous units and dermal vascularity in CRABP-II knock-out compared with wild-type mice. Ultrastructural investigation documented reduced number and secretion of epidermal lamellar bodies in CRABP-II knock-out compared with wild-type mice. Cultured CRABP-II knock-out-derived dermal fibroblasts proliferated less and showed reduced levels of TGF-β signal-related genes, Col1A1, Col1A2, and increased MMP2 transcripts compared with those from wild-type. Our data strongly support the hypothesis that a reduction of CRABP-II expression accelerates and promotes skin aging, and suggest CRABP-II as a novel target to improve the efficacy of retinoid-mediated anti-aging therapies.

Highlights

Skin aging is a biological process consisting in two types: intrinsic or chronological aging, and extrinsic aging or photoaging [1]
We investigated for the first time the role of CRABP-II expression in skin aging
We documented that reduced CRABP-II expression characterizes human and mouse aged skin and loss of CRABP-II gene leads to a premature and a more severe skin aging involving both dermal and hypodermal compartments

Summary

Introduction

Skin aging is a biological process consisting in two types: intrinsic or chronological aging, and extrinsic aging or photoaging [1]. Human skin converts vitamin A (retinol) to its biologically active metabolite all-trans retinoic acid (atRA) [12] The latter contributes to control cell growth and differentiation as well as to maintain skin homeostasis [13]. Sun-exposed and sun-protected adult skin received equal beneficial effect from atRA therapy, with beneficial effects on keratinocyte proliferation and dermal collagen production, whereas neonatal skin was unresponsive [3]. These findings suggest the selective efficacy of retinoid treatment in aged skin [16, 19]. We investigated CRABP-II expression in the skin of aged donors and the effects of CRABP-II loss on skin aging in mice

Methods

Results

Conclusion