Inhibition of Type I Procollagen Synthesis by Damaged Collagen in Photoaged Skin and by Collagenase-Degraded Collagen in Vitro

Abstract

Type I and type III procollagen are reduced in photodamaged human skin. This reduction could result from increased degradation by metalloproteinases and/or from reduced procollagen synthesis. In the present study, we investigated type I procollagen production in photodamaged and sun-protected human skin. Skin samples from severely sun-damaged forearm skin and matched sun-protected hip skin from the same individuals were assessed for type I procollagen gene expression by in situ hybridization and for type I procollagen protein by immunostaining. Both mRNA and protein were reduced (ϳ65 and 57%, respectively) in photodamaged forearm skin compared to sun-protected hip skin. We next investigated whether reduced type I procollagen production was because of inherently reduced capacity of skin fibroblasts in severely photodamaged forearm skin to synthesize procollagen, or whether contextual influences within photodamaged skin act to down-regulate type I procollagen synthesis. For these studies, fibroblasts from photodamaged skin and matched sunprotected skin were established in culture. Equivalent numbers of fibroblasts were isolated from the two skin sites. Fibroblasts from the two sites had similar growth capacities and produced virtually identical amounts of type I procollagen protein. These findings indicate that the lack of type I procollagen synthesis in sun-damaged skin is not because of irreversible damage to fibroblast collagen-synthetic capacity. It follows, therefore, that factors within the severely photodamaged skin may act in some manner to inhibit procollagen production by cells that are inherently capable of doing so. Interactions between fibroblasts and the collagenous extracellular matrix regulate type I procollagen synthesis. In sun-protected skin, collagen fibrils exist as a highly organized matrix. Fibroblasts are found within the matrix, in close apposition with collagen fibers. In photodamaged skin, collagen fibrils are shortened, thinned, and disorganized. The level of partially degraded collagen is ϳ3.6-fold greater in photodamaged skin than in sun-protected skin, and some fibroblasts are surrounded by debris. To model this situation, skin fibroblasts were cultured in vitro on intact collagen or on collagen that had been partially degraded by exposure to collagenolytic enzymes. Collagen that had been partially degraded by exposure to collagenolytic enzymes from either bacteria or human skin underwent contraction in the presence of dermal fibroblasts, whereas intact collagen did not. Fibroblasts cultured on collagen that had been exposed to either source of collagenolytic enzyme demonstrated reduced proliferative capacity (22 and 17% reduction on collagen degraded by bacterial collagenase or human skin collagenase, respectively) and synthesized less type I procollagen (36 and 88% reduction, respectively, on a per cell basis). Taken together, these findings indicate that 1) fibroblasts from photoaged and sun-protected skin are similar in their capacities for growth and type I procollagen productio...

Introduction to skin aging

“…30 While the mechanism of wrinkle formation is not entirely understood, 44 there is general atrophy of the extracellular matrix, accompanied by fewer fibroblasts, and with reduced synthetic abilty. 62, 63 Photo-aged skin exhibit histological features of chronic inflammation without significant evidence of clinical or molecular abnormalities. [64][65][66] Collagen is the body's most abundant protein.…”

In-vitro Characterization of Silk Sericin as an Anti-aging Agent

“…The sun damages the skin and accelerates the aging process. UV irradiation initiates molecular responses in human skin by the generation of reactive oxygen species (ROS) (Groß et al, 1999), activation of multiple cytokine and growth factor cell surface receptors, including epidermal growth factor receptor (EGF-R) (Varani et al, 2001), tumor necrosis factor-α receptor (TGF-α) (Dy et al, 1999), and activating protein-1 (AP-1) (Angel et al, 2001). These regulate the expression of many genes involved in cellular growth and differentiation, and the transcription of several matrix metalloproteases (MMPs) family members (Fisher & Voorhees, 1998), and also play some roles in negatively regulating type I procollagen transcription (Bornstein, 1996).…”

Mechanistic Effects of Long-Term Ultraviolet B Irradiation Induce Epidermal and Dermal Changes in Human Skin Xenografts

“…In photoaged skin, the concomitant reductions of collagen I and III occur as procollagen synthesis subsides and the existed dermal collagen degrades because of the disproportionate expression of MMP-1. [25][26][27][28] The reduction of collagens VII and IV at the dermo-epidermal junction has been also reported in the pronounced wrinkling skin. 29 In hairless mouse, repetitive UVB exposure has been reported to escalate the degradation of collagens VII and IV by up-regulating MMP-2 and MMP-9 expression.…”