Gasdermin D promotes hyperuricemia-induced renal tubular injury through RIG-I/caspase-1 pathway

Lisha Ma; Ruiqin Shen; Jie Jiao; Xiadong Lin; Bin Zhai; Aiping Xu; Hao Luo; Limin Lu; Decui Shao

doi:10.1016/j.isci.2023.108463

Gasdermin D promotes hyperuricemia-induced renal tubular injury through RIG-I/caspase-1 pathway

iScience. 2023 Nov 14;26(12):108463. doi: 10.1016/j.isci.2023.108463. eCollection 2023 Dec 15.

Authors

Lisha Ma¹, Ruiqin Shen¹, Jie Jiao¹, Xiadong Lin¹, Bin Zhai¹, Aiping Xu¹, Hao Luo¹, Limin Lu², Decui Shao¹

Affiliations

¹ Cell Electrophysiology Laboratory, Wannan Medical College, 22 Wenchangxi Road, Wuhu 241002, China.
² Department of Physiology and Pathophysiology, Shanghai Medical College, Fudan University, 138 Yixueyuan Road, Shanghai 200032, China.

Abstract

Renal tubular epithelial cells injury is one of the most important pathological features in hyperuricemic nephropathy (HN). However, the involvement of gasdermin D (GSDMD)-mediated pyroptosis in HN remains obscure. We found GSDMD was upregulated in the kidney tissue of HN mice, which was accompanied by the loss of renal function, renal tubular fibrosis, and reduced body weight. These changes in HN mice were inhibited by GSDMD knockout. Knockdown of GSDMD inhibited the high uric acid-induced injury in cultured cells (NRK-52E). Mechanistically, co-immunoprecipitation showed that RIG-I exist in a complex with caspase-1. Overexpression of RIG-I induced increased expression of caspase-1 protein and caspase-1 activity. Caspase-1 interference significantly reduced the increase of caspase-1 activity and IL-1β production caused by RIG-I overexpression. Knockdown of RIG-I or caspase-1 decreased high uric acid-induced injury in NRK-52E. This work illustrates that targeting the RIG-I/caspase-1/GSDMD may provide potential therapeutic benefits to HN.

Keywords: Biological sciences; Natural sciences; Pharmacology; Physiology.