iProXProteomicsTiannan GuoHomo Sapienshttp://www.iprox.org/page/project.html?id=IPX0009031000guotiannan@westlake.edu.cnWestlake Center for Intelligent Proteomics, Westlake Laboratory of Life Sciences and BiomedicineiProXCalciphylaxis (calcific uremic arteriolopathy, CUA) is a rare, fatal disorder primarily affecting chronic kidney disease patients, characterized by microvascular calcification, thrombosis, and skin necrosis. In a discovery cohort (3 CUA, 10 uremic), plasma proteomics identified Thrombospondin-1 (THBS1) as the top upregulated hub in CUA, significantly reduced after human amnion-derived mesenchymal stem cell (hAMSC) therapy, alongside latent TGF-β binding protein 1, both linked to coagulation and wound healing. <i>In vitro</i> proteomics indicated that THBS1/TGF-β1 blockade impaired CUA serum-induced endothelial adhesion and coagulation. ELISA in combined discovery and validation cohorts (8 CUA, 20 uremic) confirmed this reduction post-treatment (6 patients), independent of systemic inflammation. Multiplex immunofluorescence revealed THBS1 and CD47 co-localized with CD31 and integrin β3 in injured microvessels. A human microvascular chip showed that THBS1 inhibition or hAMSC-conditioned medium alleviates injury. These findings implicate THBS1 as a key factor and potential biomarker in calciphylaxis, suggesting hAMSC therapy as a promising mechanism-based approach.<h4>Video abstract</h4>Proteomics and human microchips identify Thrombospondin-1 as a potential biomarker for calciphylaxis stem cell therapy.Hu Jiaying J, Lu Shijiu S, Qin Lianju L, Sun Yaoting Y, Ye Xiaoxue X, Lin Qinyi Q, Zhang Jing J, Zeng Ming M, Wu Jingjing J, Liu Kang K, Zhu Jingfeng J, Zhang Ling L, Chen Feng F, Chen Zaozao Z, Xu Shihui S, Xue Zhangzhi Z, Yu Yongwu Y, Li Lu L, Ge Weigang W, Gu Zhongze Z, Li Cui C, Su Zhonglan Z, Luo Dan D, Tang Shaowen S, Tang Xinfang X, Ji Wuziyi W, Bian Anning A, Liao Meihua M, Fang Guicun G, Ma Xiang X, Ning Song S, Cui Yugui Y, Jiang Chunyan C, Wu Huimin H, Zhao Baiqiao B, Wang Xiuqin X, Liang Ningxia N, Xu Tingyu T, Liu Jiayin J, Liu Yun Y, Guo Tiannan T, Zhu Yi Y, Wang Ningning NfalseProteomics and Human Microchips Identify Thrombospondin-1 as a Potential Biomarker for Calciphylaxis Stem Cell TherapyCalciphylaxis, also known as calcific uremic arteriolopathy (CUA), is a rare disease with high mortality rate. We effectively rescued CUA patients with novel human amnion-derived mesenchymal stem cell (hAMSC) therapy. Due to the heterogeneity of cutaneous lesion, it is imperative to identify non-invasive biomarkers.Thu May 14 00:00:00 GMT+01:00 2026PXD078388960642382992