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This study aimed to explore the effect of cGAS-STING signaling pathway on the MMT process in peritoneal mesothelial cells. The expressions of cGAS, STING, \u03b1-SMA, and Vimentin in HMrSV5 cells treated with high glucose were analyzed using WB. Subsequently, si-cGAS and the cGAS inhibitor RU.521 were employed to intervene in HMrSV5 cells. qPCR was utilized to evaluate the expression levels of genes involved in the cGAS-STING signaling pathway (cGAS, STING, IRF3, TBK1) and MMT-related genes (E-cadherin, Vimentin, \u03b1-SMA, TGF-\u03b21). The protein expressions of the cGAS-STING signaling pathway and MMT-related proteins were detected by WB. The invasive capacity of cells in each cell was assessed using a Transwell assay, and the levels of pro-inflammatory cytokines (IL-6, TNF-\u03b1) in the supernatants of each cell were measured by ELISA. In the present study, we found that the expressions of cGAS, p-STING\/STING, p-IRF3\/IRF3, and p-TBK1\/TBK1 proteins were significantly upregulated in HG-treated HMrSV5 cells. Furthermore, the activation of the cGAS-STING signaling pathway could be effectively suppressed in HMrSV5 cells transfected with si-cGAS or treated with RU.521. Additionally, treatment with si-cGAS or RU.521 not only attenuated the invasive capacity of HMrSV5 cells but also decreased the levels of pro-inflammatory cytokines and inhibited the expression of MMT-related markers. Suppression of the cGAS-STING signaling pathway mitigates HG-induced MMT in the human peritoneal mesothelial cell line HMrSV5.<\/jats:p>","DOI":"10.1007\/s11626-025-01107-1","type":"journal-article","created":{"date-parts":[[2025,8,28]],"date-time":"2025-08-28T15:44:42Z","timestamp":1756395882000},"page":"1097-1106","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Inhibition of cGAS-STING signaling pathway alleviates high glucose-induced mesothelial-mesenchymal transition in human peritoneal mesothelial cell line HMrSV5"],"prefix":"10.1007","volume":"61","author":[{"given":"Fuxing","family":"Dong","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luli","family":"Zheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fuyuan","family":"Hong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,8,28]]},"reference":[{"key":"1107_CR1","doi-asserted-by":"publisher","first-page":"2379","DOI":"10.1007\/s00210-023-02450-4","volume":"396","author":"Y Bai","year":"2023","unstructured":"Bai Y, Wang L, TingYang WL, Ge W (2023) Silymarin ameliorates peritoneal fibrosis by inhibiting the TGF-\u03b2\/Smad signaling pathway. 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