Jornal de Pesquisa em Dermatologia Clínica e Experimental
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Resveratrol Inhibits Proliferation and Promotes Apoptosis of Keloid Fibroblasts by Targeting HIF-1α

Loubin Si, Qin Han, Xiao Long, Fei Long, Robert Chunhua Zhao, Jiuzhuo Huang, Zhifei Liu, Ru Zhao, Hailin Zhang, Xiaojun Wang

Keloid is characterized by red, tickling, hard and irregular raised tissues, and tends to outgrow its origin. It occurs frequently in young adults and appears as refractory to prevailing therapies. Although histological studies have revealed striking similarities of keloids with cancer, such as uncontrolled cell growth, and many of the therapies in clinical practice including -fluorouracil and tamoxifen, excision, and radiation therapy were borrowed from cancer management, the etiology of keloid has remained to be explored to provide insights for developing effective therapeutic modalities. Hypoxic stress around tumors was frequently reported as conferring growth momentum to tumor cells. The hypoxia caused by fast growing of keloid fibroblasts may also be a risk factor that antagonizes therapies. Resveratrol has received intense attention in cancer researches since its anti-proliferative effect on human pulmonary artery smooth muscle cells were revealed. In this study, we first revealed that hypoxia promotes proliferation and inhibit apoptosis of keloid fibroblasts, which highlights the potential obstacle in treating keloids. Further, we demonstrated resveratrol could reverse the effect of hypoxia on keloids, which involves down-regulation of HIF-1α. Moreover, the collagen synthesis of keloid fibroblasts was also inhibited by resveratrol, which was corresponding with HIF-1α suppression. These results provide complementary evidence to the multiple molecular signalings controlled by resveratrol and suggest a pathway implicates resveratrol to regulate expression of procollagen expression via HIF-1α.