Syndecan-1 shedding destroys epithelial adherens junctions through STAT3 after renal ischemia/reperfusion injury.

Adherens junctions between tubular epithelial cells are disrupted in renal ischemia/reperfusion (I/R) injury. Syndecan-1 (SDC-1) is involved in maintaining cell morphology. We aimed to study the role of SDC-1 shedding induced by renal I/R in the destruction of intracellular adherens junctions. We found that SDC-1 shedding was increased while the expression of E-cadherin was decreased. This observation was accompanied by the activation of STAT3 in the kidneys. Inhibiting the shedding of SDC-1 induced by I/R could alleviate this effect. Mild renal I/R could induce more severe renal injury, lower E-cadherin expression, damaged cell junctions, and activated STAT3 in knockout mice with the tubule-specific deletion of SDC-1 mice. The results in vitro were consistent with those in vivo. Inhibiting the shedding of SDC-1 could alleviate the decreased expression of E-cadherin and damage of cell adherens junctions through inhibiting the activation of STAT3 during ischemic acute kidney injury. © 2023 The Author(s).

Citation

Man Guo, Daoqi Shen, Yiqi Su, Jiarui Xu, Shuan Zhao, Weidong Zhang, Yaqiong Wang, Wuhua Jiang, Jialin Wang, Xuemei Geng, Xiaoqiang Ding, Xialian Xu. Syndecan-1 shedding destroys epithelial adherens junctions through STAT3 after renal ischemia/reperfusion injury. iScience. 2023 Nov 17;26(11):108211

PMID: 37942007

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