ASC-J9 Blocks Cell Proliferation and Extracellular Matrix Production of Keloid Fibroblasts through Inhibiting STAT3 Signaling

Yi Kai Hong, Chen Han Wu, Yu Chen Lin, Yu Lun Huang, Kuo Shu Hung, Tsung Pin Pai, Yen Ting Liu, Tzu Chi Chen, Hardy Chan, Chao Kai Hsu

研究成果: Article同行評審

1 引文 斯高帕斯(Scopus)

摘要

Keloids are a fibrotic skin disorder caused by abnormal wound healing and featuring the activation and expansion of fibroblasts beyond the original wound margin. Signal transducer and activator of transcription 3 (STAT3) has been found to mediate the biological functions of keloid fibroblasts (KFs). Therefore, we aimed to demonstrate whether ASC-J9, an inhibitor of STAT3 phosphorylation, can suppress the activation of KFs. Western blotting results showed that ASC-J9 inhibited the levels of COL1A1 and FN1 proteins, which were upregulated in KFs, by decreasing the expression of pSTAT3 and STAT3. RNA sequencing and in vitro studies further demonstrated that ASC-J9 treatment of KFs reduced cell division, inflammation, and ROS generation, as well as extracellular matrix (ECM) synthesis. ELISA assays verified that ASC-J9 treatment significantly mitigated IL-6 protein secretion in KFs. Transmission electron microscopy images revealed that ASC-J9 induced the formation of multilamellar bodies in KFs, which is associated with autophagy-related signaling. These results suggested that inhibiting a vicious cycle of the ROS/STAT3/IL-6 axis by ASC-J9 may represent a potential therapeutic approach to suppress cell proliferation and ECM production in KFs.

原文English
文章編號5549
期刊International journal of molecular sciences
23
發行號10
DOIs
出版狀態Published - 2022 5月 1

All Science Journal Classification (ASJC) codes

  • 催化
  • 分子生物學
  • 光譜
  • 電腦科學應用
  • 物理與理論化學
  • 有機化學
  • 無機化學

指紋

深入研究「ASC-J9 Blocks Cell Proliferation and Extracellular Matrix Production of Keloid Fibroblasts through Inhibiting STAT3 Signaling」主題。共同形成了獨特的指紋。

引用此