A Novel Truncated TGF-β Receptor II Downregulates Collagen Synthesis and TGF-β I Secretion of Keloid Fibroblasts.

Hypertrophic scars and keloid are dermal proliferative disorders in wound healing. Transforming growth factor β (TGF-β) has been implicated in scar formation through the activation of fibroblasts and the acceleration of collagen deposition. Our study aimed to design a novel truncated (27-123 residues) type II TGF-β receptor (tTGFβRII) and to determine its effects on the proliferation of keloid fibroblasts and the collagen synthesis as well as TGF-β I expression of the cells. The coding sequences of TGF-β I and tTGFβRII were amplified using RT-PCR and then cloned into pGBKT7 and pGADT7 vectors. A yeast two-hybrid experiment and a glutathione S-transferase (GST)-pull down assay were performed to verify the affinity of tTGFβRII to TGF-β I. Our results indicated that treatment with tTGFβRII inhibited the growth of keloid fibroblasts and suppressed the synthesis of type I collagen in keloid fibroblasts in a concentration-dependent manner. Moreover, northern and western blot analysis revealed a decline of the TGF-β I expression at both mRNA and protein levels after exposure to 5, 10 or 20 μg/ml of tTGFβRII. Together, our data suggested that the exogenous tTGFβRII can efficiently trap TGF-β I from access to wild-type receptors and can suppress TGF-β I triggered signals. Thus it may potentially be clinically applied to scar therapy. [ABSTRACT FROM AUTHOR]