Wound healing: a role for HDACs in inhibition of fibroblast proliferation through repression of PDGF receptor-alpha. Focus on 'Repression of PDGF-R-alpha after cellular injury involves TNF-alpha, formation of a c-Fos-YY1 complex, andnegative regulation by HDAC'

摘要

the role of fibroblasts in wound healing has been studied for many years. These cells play a critical role in the regenerative process, and efforts to target processes that regulate fibroblast function and phenotype provide attractive therapeutic possibilities. However, fibroblasts can play a complex role, with perpetual activation being associated with chronic inflammation, fibrosis, and progression of tumors. Previous studies have focused on identifying factors that alter the recruitment of these cells. In addition, the conversion of fibroblasts to profibrogenic myofibroblasts has been identified as a key event in wound healing. There is clearly a balance between appropriate fibroblast activation and the fibrosis that results from their continuing activation. Multiple growth factors have been implicated in fibroblast migration and activation, but much attention has been recently focused on the platelet-derived growth factor (PDGF) family of growth factors and their cognate receptors (PDGFR). This family signals through cell surface receptors that are members of the receptor tyrosine kinase family of receptors. Fibroblasts express both isoforms of the PDGF receptor, PDGFR-alpha and PDGFR-beta, which form hetero- and homodimers and differ in their ability to respond to isoforms of PDGF (6). PDGFR-a binds all of the isoforms with the exception of PDGF-DD. Previous studies have shown that PDGFR-a expression is reduced in the setting of dermal injury, and impaired wound healing is associated with decreased expression of this receptor (1). However, the molecular mechanisms mediating these effects have not been well defined.