Co-transfection of hepatocyte growth factor and truncated TGF-β type II receptor inhibit scar formation

Wound scarring remains a major challenge for plastic surgeons. Transforming growth factor (TGF)-beta plays a key role in the process of scar formation. Previous studies have demonstrated that truncated TGF-beta type II receptor (t-TGF-beta RII) is unable to continue signal transduction but is still capable of binding to TGF-beta, thereby blocking the TGF-beta signaling pathway. Hepatocyte growth factor (HGF) is a multifunctional growth factor that promotes tissue regeneration and wound healing. Theoretically, the combination of HGF and t-TGF-beta RII would be expected to exert a synergistic effect on promoting wound healing and reducing collagen formation. In the present study, lentivirus-mediated transfection of the two genes (t-TGF-beta RII/HGF) into fibroblasts in vitro and in a rat model in vivo was used. The results demonstrated that the expression of t-TGF-beta RII and HGF in NIH-3T3 cells was successfully induced. The expression of both molecules significantly reduced collagen I and III expression, and also inhibited fibroblast proliferation. Furthermore, histological examination and scar quantification revealed less scarring in the experimental wound in a rat model. Moreover, on macroscopic inspection, the experimental wound exhibited less visible scarring compared with the control. Therefore, the present study demonstrated that the combination gene therapy of t-TGF-beta RII and HGF promoted wound healing, with less scarring and more epithelial tissue formation, not only by suppressing the overgrowth of collagen due to its antifibrotic effect, but also by promoting tissue regeneration.