Peroxisome proliferator-activated receptor-gamma (PPAR-gamma) ligands have been recently reported to have beneficial effects on organ fibrosis. However, their effects on extracellular matrix (ECM) turnover in hypertrophic scar fibroblasts (HSFs), and the related molecular mechanisms are unknown. HSFs were cultured and exposed to different concentration PPAR-gamma ligands in the presence of transforming growth factor-beta1 (TGF-beta1). In growth-arrested HSFs, a PPAR-gamma natural ligand (15-deoxy-D12,14-prostaglandin J2, 15d-PGJ2) and a synthetic ligand (GW7845) dose-dependently attenuated TGFbeta1-induced expression of Connective tissue growth factor (CTGF), collagens and fibronectin. Furthermore, the suppression of CTGF mRNA and protein expression are relieved by pretreatment with an antagonist of PPAR-gamma (GW9662). Moreover, GW7845 and 15d-PGJ2 partially inhibited the expression and phosphorylation of the TGF-beta1/Smad pathway. These results suggest that in TGFbeta1-stimulated HSFs, PPAR-gamma ligands caused an antiproliferative effect and reduced ECM production through mechanisms that included reducing CTGF expression, and a crosstalk between PPAR-gamma and Smad may be involved in the inhibitory effects of PPAR-gamma ligands.

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Random-pattern skin flap is widely used in tissue reconstruction. However, necrosis occurring in the distal part of the flap limits its clinical application to some extent. Activation of autophagy has been considered as an effective approach to enhance the survival of skin flaps. Pseudoginsenoside F11 (PF11), an ocotillol-type saponin, is an important component of Panax quinquefolium which has been shown to confer protection against cerebral ischemia and alleviate oxidative stress. However, it is currently unknown whether PF11 induces autophagy to improve the survival of skin flaps. In this study, we investigated the effects of PF11 on blood flow and tissue edema. The results of histological examination and western blotting showed that PF11 enhanced angiogenesis, alleviated apoptosis and oxidative stress, thereby improving the survival of the flap. Further experiments showed that PF11 promoted nuclear translocation of TFEB and by regulating the phosphorylation of AMPK. In summary, this study demonstrates that PF11 activates autophagy through the AMPK-TFEB signal pathway in skin flaps and it could be a promising strategy for enhancing flap viability.