Pathway network of pyroptosis and its potential inhibitors in acute kidney injury

Ning Li; Yuru Wang; Xinyue Wang; Na Sun; Yan-Hua Gong

doi:10.1016/j.phrs.2021.106033

Pathway network of pyroptosis and its potential inhibitors in acute kidney injury

Pharmacol Res. 2022 Jan:175:106033. doi: 10.1016/j.phrs.2021.106033. Epub 2021 Dec 14.

Authors

Ning Li¹, Yuru Wang², Xinyue Wang², Na Sun², Yan-Hua Gong³

Affiliations

¹ Institute of Disaster and Emergency Medicine, Tianjin University, Tianjin 300072, China; State Key Laboratory of Medicinal Chemical Biology, Nankai University, Tianjin 300350, China; Tianjin Key Laboratory of Disaster Medicine Technology, Tianjin 300072, China; Wenzhou Safety (Emergency) Institute, Tianjin University, Wenzhou 325000, China.
² Institute of Disaster and Emergency Medicine, Tianjin University, Tianjin 300072, China; Tianjin Key Laboratory of Disaster Medicine Technology, Tianjin 300072, China; Wenzhou Safety (Emergency) Institute, Tianjin University, Wenzhou 325000, China.
³ Institute of Disaster and Emergency Medicine, Tianjin University, Tianjin 300072, China; Tianjin Key Laboratory of Disaster Medicine Technology, Tianjin 300072, China; Wenzhou Safety (Emergency) Institute, Tianjin University, Wenzhou 325000, China. Electronic address: gongyanhua@tju.edu.cn.

PMID: 34915124
DOI: 10.1016/j.phrs.2021.106033

Abstract

Acute kidney injury (AKI) is a worldwide problem, and there is no effective drug to eliminate AKI. The death of renal cells is an important pathological basis of intrinsic AKI. At present, targeted therapy for TEC death is a research hotspot in AKI therapy. There are many ways of cell death involved in the occurrence and development of AKI, such as apoptosis, necrosis, ferroptosis, and pyroptosis. This article mainly focuses on the role of pyroptosis in AKI. The assembly and activation of NLRP3 inflammasome is a key event in the occurrence of pyroptosis, which is affected by many factors, such as the activation of the NF-κB signaling pathway, mitochondrial instability and excessive endoplasmic reticulum (ER) stress. The activation of NLRP3 inflammasome can trigger its downstream inflammatory cytokines, which will lead to pyroptosis and eventually induce AKI. In this paper, we reviewed the possible mechanism of pyroptosis in AKI and the potential effective inhibitors of various key targets in this process. It may provide potential therapeutic targets for novel intrinsic AKI therapies based on pyroptosis, so as to develop better therapeutic strategies.

Keywords: Ac-FLTD-CMK (PubChem CID: 155906572); Acute kidney injury; Bay 11–7082 (PubChem CID: 5353431); C16 (PubChem CID: 6490494); CY-09 (PubChem CID: 75070350); Dimethyl fumarate (PubChem CID: 637568); Disulfiram (PubChem CID: 3117); Glycyrrhizin (PubChem CID: 14982); JC124 (PubChem CID: 117715670); Lenalidomide (PubChem CID: 216326); MCC950 (PubChem CID: 9910393); MNS (PubChem CID: 672296); Mdivi-1 (PubChem CID: 3825829); NLRP3 inflammasome; Necrosulfonamide (PubChem CID: 1566236); OLT1177 (PubChem CID: 12714644); Oridonin (PubChem CID: 5321010); Parthenolide (PubChem CID: 7251185); Pyroptosis; Pyroptosis inhibitor; RRx-001 (PubChem CID: 15950826); Salvianolic acid B (PubChem CID: 6451084); Signaling pathway; Tranilast (PubChem CID: 5282230); VX-740 (PubChem CID: 153270); VX-765 (PubChem CID: 11398092); Vitamin D (PubChem CID: 5280795); z-VAD-fmk (PubChem CID: 8714607).

Publication types

Research Support, Non-U.S. Gov't
Review

MeSH terms

Acute Kidney Injury / drug therapy*
Acute Kidney Injury / metabolism
Animals
Humans
Pyroptosis*
Signal Transduction