Remdesivir alleviates skin fibrosis by suppressing TGF-β1 signaling pathway

• Published in: PloS one Vol. 19; no. 7; p. e0305927
• Main Authors: Zhang, Jianwei, Zhang, Xiujun, Guo, Xiaowei, Li, Wenqi, Zhang, Tiantian, Chai, Dan, Liu, Yuming, Chen, Li, Ai, Xiaoyu, Zhou, Tianyuan, Wei, Wenguo, Gu, Xiaoting, Li, Xiaohe, Zhou, Honggang
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 18.07.2024; Public Library of Science (PLoS)
• Subjects: 1-Phosphatidylinositol 3-kinase; Activation analysis; Adenosine Monophosphate - analogs & derivatives; Adenosine Monophosphate - metabolism; Adenosine Monophosphate - pharmacology; AKT protein; Alanine - analogs & derivatives; Alanine - pharmacology; Alanine - therapeutic use; Animals; Antiviral Agents - pharmacology; Antiviral drugs; Autophagy; Autophagy - drug effects; Biology and Life Sciences; Bleomycin; Cell culture; Extracellular matrix; Fibroblasts; Fibroblasts - drug effects; Fibroblasts - metabolism; Fibrosis; Fibrosis - drug therapy; Humans; In vivo methods and tests; Keloid - drug therapy; Keloid - metabolism; Keloid - pathology; Male; Medicine and Health Sciences; Mice; Penicillin; Phosphatidylinositol 3-Kinases - metabolism; Proto-Oncogene Proteins c-akt - metabolism; Research and Analysis Methods; RNA polymerase; Signal transduction; Signal Transduction - drug effects; Skin - drug effects; Skin - metabolism; Skin - pathology; Skin diseases; Smad protein; Smad Proteins - metabolism; TOR protein; TOR Serine-Threonine Kinases - metabolism; Transforming Growth Factor beta1 - metabolism; Transforming growth factor-b1; Beijing China; United States > US; China
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0305927

Fibrotic skin diseases, such as keloids, are pathological results of aberrant tissue healing and are characterized by overgrowth of dermal fibroblasts. Remdesivir (RD), an antiviral drug, has been reported to have pharmacological activities in a wide range of fibrotic diseases. However, whether RD function on skin fibrosis remains unclear. Therefore, in our study, we explored the potential effect and mechanisms of RD on skin fibrosis both in vivo and in vitro. As expected, the results demonstrated that RD alleviated BLM-induced skin fibrosis and attenuates the gross weight of keloid tissues in vivo. Further studies suggested that RD suppressed fibroblast activation and autophagy both in vivo and in vitro. In addition, mechanistic research showed that RD attenuated fibroblasts activation by the TGF-β1/Smad signaling pathway and inhibited fibroblasts autophagy by the PI3K/Akt/mTOR signaling pathway. In summary, our results demonstrate therapeutic potential of RD for skin fibrosis in the future.