Proteomics and human microchips identify Thrombospondin-1 as a potential biomarker for calciphylaxis stem cell therapy

  • iScience. 2026 Jun 19;29(7):116388. doi: 10.1016/j.isci.2026.116388.
Jiaying Hu  1  2 ,  Shijiu Lu  1  2  3 ,  Lianju Qin  4 ,  Yaoting Sun  5  6  7 ,  Xiaoxue Ye  1  2  8 ,  Qinyi Lin  1 ,  Jing Zhang  2 ,  Ming Zeng  2 ,  Jingjing Wu  2 ,  Kang Liu  2 ,  Jingfeng Zhu  2 ,  Ling Zhang  9 ,  Feng Chen  10 ,  Zaozao Chen  11  12  13 ,  Shihui Xu  12 ,  Zhangzhi Xue  5  6  7 ,  Yongwu Yu  14 ,  Lu Li  5  6  7 ,  Weigang Ge  15 ,  Zhongze Gu  11 ,  Cui Li  1  2 ,  Zhonglan Su  16 ,  Dan Luo  16 ,  Shaowen Tang  11 ,  Xinfang Tang  1  2 ,  Wuziyi Ji  17 ,  Anning Bian  2 ,  Meihua Liao  18 ,  Guicun Fang  18 ,  Xiang Ma  4 ,  Song Ning  4 ,  Yugui Cui  4 ,  Chunyan Jiang  4 ,  Huimin Wu  4 ,  Baiqiao Zhao  1  2  19 ,  Xiuqin Wang  20 ,  Ningxia Liang  21 ,  Tingyu Xu  22 ,  Jiayin Liu  4 ,  Yun Liu  23 ,  Tiannan Guo  5  6  7 ,  Yi Zhu  6 ,  Ningning Wang  1  2  24
Affiliations
  • 1. Division of Nephrology, Department of Geriatrics, the First Affiliated Hospital with Nanjing Medical University, Jiangsu Province Hospital, Nanjing 210029, China.
  • 2. Department of Nephrology, the First Affiliated Hospital with Nanjing Medical University, Jiangsu Province Hospital, Nanjing 210029, China.
  • 3. Department of Nephrology, The Affiliated Huaihai Hospital of Xuzhou Medical University, Xuzhou 221004, China.
  • 4. State Key Laboratory of Reproductive Medicine and Offspring Health, Center of Clinical Reproductive Medicine, the First Affiliated Hospital with Nanjing Medical University, Jiangsu Province Hospital, Nanjing 210029, China.
  • 5. School of Medicine, Westlake University, Hangzhou 310024, China.
  • 6. Westlake Center for Intelligent Proteomics, Westlake Laboratory of Life Sciences and Biomedicine, Hangzhou 310024, China.
  • 7. Research Center for Industries of the Future, School of Life Sciences, Westlake University, Hangzhou 310024, China.
  • 8. Department of Nephrology, Putuo District Central Hospital of Shanghai, Shanghai 200063, China.
  • 9. Department of Nephrology, China-Japan Friendship Hospital, Beijing 100029, China.
  • 10. Department of Epidemiology and Biostatistics, School of Public Health, Nanjing Medical University, Nanjing 211166, China.
  • 11. State Key Laboratory of Digital Medical Engineering, School of Biological Science and Medical Engineering, Southeast University, Nanjing 210096, China.
  • 12. Jiangsu Avatarget Biotechnology Co., Ltd., Nanjing 211100, China.
  • 13. Southeast University Nanjing Jiangbei New Area Innovation Institute, Nanjing 211800, China.
  • 14. Department of Nephrology, ChuiYangLiu Hospital Affiliated to Tsinghua University, Beijing 100022, China.
  • 15. Westlake Omics (Hangzhou) Biotechnology Co., Ltd., Hangzhou 310024, China.
  • 16. Department of Dermatology, the First Affiliated Hospital with Nanjing Medical University, Jiangsu Province Hospital, Nanjing 210029, China.
  • 17. Nanjing University of Chinese Medicine, Nanjing 210023, China.
  • 18. Biomedical Research Core Facilities Platform, Westlake University, Hangzhou 310024, China.
  • 19. Department of Nephrology, the First People's Hospital of Lianyungang, Lianyungang 222002, China.
  • 20. Department of International Cooperation, the First Affiliated Hospital with Nanjing Medical University, Jiangsu Province Hospital, Nanjing 210029, China.
  • 21. Academy of Clinical and Translational Research, the First Affiliated Hospital with Nanjing Medical University, Jiangsu Province Hospital, Nanjing 210029, China.
  • 22. Department of Information, the First Affiliated Hospital with Nanjing Medical University, Jiangsu Province Hospital, Nanjing 210029, China.
  • 23. Division of Endocrinology, Department of Geriatrics, the First Affiliated Hospital with Nanjing Medical University, Jiangsu Province Hospital, Nanjing 210029, China.
  • 24. Jiangsu Provincial Key Laboratory of Biological Therapy for Organ Failure, Nanjing Medical University, Nanjing 211166, China.
PMID: 42382992 DOI: 10.1016/j.isci.2026.116388
Abstract

Calciphylaxis (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. In vitro 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.

Keywords
Health sciences; Medicine; Proteomics.
Products