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

Man Guo; Daoqi Shen; Yiqi Su; Jiarui Xu; Shuan Zhao; Weidong Zhang; Yaqiong Wang; Wuhua Jiang; Jialin Wang; Xuemei Geng; Xiaoqiang Ding; Xialian Xu

doi:10.1016/j.isci.2023.108211

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

iScience. 2023 Oct 14;26(11):108211. doi: 10.1016/j.isci.2023.108211. eCollection 2023 Nov 17.

Authors

Man Guo^{1

2

3

4

5}, Daoqi Shen^{1

2

3

4

5}, Yiqi Su^{1

2

3

4

5}, Jiarui Xu^{1

2

3

4

5}, Shuan Zhao^{1

2

3

4

5}, Weidong Zhang^{1

2

3

4

5}, Yaqiong Wang^{1

2

3

4

5}, Wuhua Jiang^{1

2

3

4

5}, Jialin Wang^{1

2

3

4

5}, Xuemei Geng^{1

2

3

4

5}, Xiaoqiang Ding^{1

2

3

4

5}, Xialian Xu^{1

2

3

4

5}

Affiliations

¹ Division of Nephrology, Zhongshan Hospital, Fudan University, Shanghai, China.
² Shanghai Medical Center of Kidney Disease, Shanghai, China.
³ Shanghai Institute of Kidney and Dialysis, Shanghai, China.
⁴ Key Laboratory of Kidney and Blood Purification, Shanghai, China.
⁵ Hemodialysis quality control center of Shanghai, Shanghai, China.

Abstract

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.

Keywords: Medical Microbiology; Nephrology.