Activated SOX9+renal epithelial cells promote kidney repair through secreting factors

被引:9
作者
Nie, Hao [1 ]
Zhao, Zixian [1 ]
Zhou, Dewei [1 ]
Li, Dandan [1 ]
Wang, Yujia [1 ,2 ]
Ma, Yu [2 ]
Liu, Xutao [3 ]
Zuo, Wei [1 ,2 ,4 ,5 ]
机构
[1] Tongji Univ, East Hosp, Sch Med, Shanghai, Peoples R China
[2] Super Organ R&D Ctr, Regend Therapeut, Shanghai, Peoples R China
[3] Univ Calif Los Angeles, Samueli Sch Engn, Los Angeles, CA USA
[4] Sichuan Univ, West China Hosp, Key Lab Transplant Engn & Immunol, Minist Hlth, Chengdu, Peoples R China
[5] Tongji Univ, Shanghai East Hosp, Sch Med, Shanghai, Peoples R China
基金
中国国家自然科学基金;
关键词
RENAL REPAIR; STEM-CELLS; SOX9; EXPRESSION; INJURY; REGENERATION; CONTRIBUTES; MARKERS; PROTECT;
D O I
10.1111/cpr.13394
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
A broad spectrum of lethal kidney diseases involves the irreversible destruction of the tubular structures, leading to renal function loss. Following injury, a spectrum of tissue-resident epithelial stem/progenitor cells are known to be activated and then differentiate into mature renal cells to replace the damaged renal epithelium. Here, however, we reported an alternative way that tissue-resident cells could be activated to secrete multiple factors to promote organ repair. At single-cell resolution, we showed that the resident SOX9+ renal epithelial cells (RECs) could expand in the acutely injured kidney of both mouse and human. Compared to other cells, the SOX9+ RECs overexpressed much more secretion related genes, whose functions were linked to kidney repair pathways. We also obtained long-term, feeder-free cultured SOX9+ RECs from human urine and analysed their secretory profile at both transcriptional and proteomic levels. Engraftment of cultured human SOX9+ RECs or injection of its conditional medium facilitated the regeneration of renal tubular and glomerular epithelium, probably through stimulating endogenous REC self-activation and mediating crosstalk with other renal cells. We also identified S100A9 as one of the key factors in the SOX9+ REC secretome. Altogether, the abilities to extensively propagate SOX9+ RECs in culture whilst concomitantly maintaining their intrinsic secretory capacity suggest their future application in cell-free therapies and regeneration medicine.
引用
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页数:16
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