Normal skin and hypertrophic scar fibroblasts differentially regulate collagen and fibronectin expression as well as mitochondrial membrane potential in response to basic fibroblast growth factor

Rui Song,Hua-De Chen,Wen Lai,Ke-Seng Zhao,Hui-Ning Bian

doi:10.1590/s0100-879x2011007500041

Abstract

Basic fibroblast growth factor (bFGF) regulates skin wound healing; however, the underlying mechanism remains to be defined. In the present study, we determined the effects of bFGF on the regulation of cell growth as well as collagen and fibronectin expression in fibroblasts from normal human skin and from hypertrophic scars. We then explored the involvement of mitochondria in mediating bFGF-induced effects on the fibroblasts. We isolated and cultivated normal and hypertrophic scar fibroblasts from tissue biopsies of patients who underwent plastic surgery for repairing hypertrophic scars. The fibroblasts were then treated with different concentrations of bFGF (ranging from 0.1 to 1000 ng/mL). The growth of hypertrophic scar fibroblasts became slower with selective inhibition of type I collagen production after exposure to bFGF. However, type III collagen expression was affected in both normal and hypertrophic scar fibroblasts. Moreover, fibronectin expression in the normal fibroblasts was up-regulated after bFGF treatment. bFGF (1000 ng/mL) also induced mitochondrial depolarization in hypertrophic scar fibroblasts (P < 0.01). The cellular ATP level decreased in hypertrophic scar fibroblasts (P < 0.05), while it increased in the normal fibroblasts following treatment with bFGF (P < 0.01). These data suggest that bFGF has differential effects and mechanisms on fibroblasts of the normal skin and hypertrophic scars, indicating that bFGF may play a role in the early phase of skin wound healing and post-burn scar formation.

Highlights

Wound healing is a dynamic and closely interactive process of various growth factors, fibroblasts, and the formation of new blood vessels and extracellular matrices
Excessive myofibroblast differentiation and extracellular matrix formation may be involved in hypertrophic scarring and formation of post-burn scars, such as fibrosis and keloids [3], resulting in hypertrophic scars, the management of which remains a challenge in clinical practice
We observed that production of type I collagen by hypertrophic scar (HS) fibroblasts was much higher than production by normal skin fibroblasts in the absence of Basic fibroblast growth factor (bFGF), while production of type I collagen by HS fibroblasts was significantly inhibited by a high dose of bFGF

Summary

Introduction

Wound healing is a dynamic and closely interactive process of various growth factors, fibroblasts, and the formation of new blood vessels and extracellular matrices. Some fibroblasts differentiate into myofibroblasts, which are principally responsible for tissue contraction, and produce extracellular matrix components. In normal human wound healing, once tissue integrity has been restored, the myofibroblasts disappear from the scar [2]. Increased activity of fibrogenic cytokines [e.g., transforming growth factor ß1 (TGF-ß1), insulin-like growth factor 1 (IGF-1), and interleukin-1] and exaggerated responses to these cytokines may play a role in post-burn scars such as fibrosis and keloids [3]. The aberrant fibroblast phenotype seems to contribute to the hypertrophic scars or post-burn scars, which may be due to the differential response of normal and HS fibroblasts to various growth factors.

Methods

Results

Conclusion