Cargando…
Hydrogen sulfide attenuates renal I/R-induced activation of the inflammatory response and apoptosis via regulating Nrf2-mediated NLRP3 signaling pathway inhibition
Renal ischemia/reperfusion (I/R) injury can lead to acute renal failure, delayed graft function and graft rejection. Nucleotide-binding oligomerization domain NOD-like receptor containing pyrin domain 3 (NLRP3)-mediated inflammation participates in the development of renal injury. Nrf2 accelerates N...
Autores principales: | , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
D.A. Spandidos
2021
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8160482/ https://www.ncbi.nlm.nih.gov/pubmed/34013370 http://dx.doi.org/10.3892/mmr.2021.12157 |
_version_ | 1783700297208561664 |
---|---|
author | Su, Yonghong Wang, Yaoqi Liu, Min Chen, Hongguang |
author_facet | Su, Yonghong Wang, Yaoqi Liu, Min Chen, Hongguang |
author_sort | Su, Yonghong |
collection | PubMed |
description | Renal ischemia/reperfusion (I/R) injury can lead to acute renal failure, delayed graft function and graft rejection. Nucleotide-binding oligomerization domain NOD-like receptor containing pyrin domain 3 (NLRP3)-mediated inflammation participates in the development of renal injury. Nrf2 accelerates NLRP3 signaling pathway activation and further regulates the inflammatory response. In addition, hydrogen sulfide serves a protective role in renal injury; however, the detailed underlying mechanism remains poorly understood. The present study investigated whether Nrf2 and NLRP3 pathway participate in hydrogen sulfide-regulated renal I/R-induced activation of the inflammatory response and apoptosis. Wild-type and Nrf2-knockout (KO) mice underwent surgery to induce renal I/R via clamping of the bilateral renal pedicles. A total of 20 mg/kg MCC950 (an NLRP3 inhibitor) was injected intraperitoneally daily for 14 days prior to surgery. Renal tissue and blood were collected from the I/R model mice to analyze NLRP3 and Nrf2 mRNA expression levels, NLRP3, PYD and CARD domain containing, caspase-1, IL-1β, Nrf2 and heme oxygenase 1 protein expression levels, cell apoptosis, the secretion of tumor necrosis factor-α, IL-1β and IL-6 cytokines and renal histopathology and function. Renal I/R activated the NLRP3 and Nrf2 signaling pathways. Conversely, MCC950 treatment inhibited activation of the NLRP3 signaling pathway, and prevented I/R-induced renal injury, release of cytokines and apoptosis in renal I/R model mice. Sodium hydrosulfide (NaHS) not only alleviated upregulation of NLRP3 protein expression levels, but also relieved renal injury, release of cytokines and cell apoptosis induced by renal I/R in wild-type mice, but not in Nrf2-KO mice. NaHS alleviated NLRP3 inflammasome activation, renal injury, the inflammatory response and cell apoptosis via the Nrf2 signaling pathway in renal I/R model mice. |
format | Online Article Text |
id | pubmed-8160482 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | D.A. Spandidos |
record_format | MEDLINE/PubMed |
spelling | pubmed-81604822021-06-01 Hydrogen sulfide attenuates renal I/R-induced activation of the inflammatory response and apoptosis via regulating Nrf2-mediated NLRP3 signaling pathway inhibition Su, Yonghong Wang, Yaoqi Liu, Min Chen, Hongguang Mol Med Rep Articles Renal ischemia/reperfusion (I/R) injury can lead to acute renal failure, delayed graft function and graft rejection. Nucleotide-binding oligomerization domain NOD-like receptor containing pyrin domain 3 (NLRP3)-mediated inflammation participates in the development of renal injury. Nrf2 accelerates NLRP3 signaling pathway activation and further regulates the inflammatory response. In addition, hydrogen sulfide serves a protective role in renal injury; however, the detailed underlying mechanism remains poorly understood. The present study investigated whether Nrf2 and NLRP3 pathway participate in hydrogen sulfide-regulated renal I/R-induced activation of the inflammatory response and apoptosis. Wild-type and Nrf2-knockout (KO) mice underwent surgery to induce renal I/R via clamping of the bilateral renal pedicles. A total of 20 mg/kg MCC950 (an NLRP3 inhibitor) was injected intraperitoneally daily for 14 days prior to surgery. Renal tissue and blood were collected from the I/R model mice to analyze NLRP3 and Nrf2 mRNA expression levels, NLRP3, PYD and CARD domain containing, caspase-1, IL-1β, Nrf2 and heme oxygenase 1 protein expression levels, cell apoptosis, the secretion of tumor necrosis factor-α, IL-1β and IL-6 cytokines and renal histopathology and function. Renal I/R activated the NLRP3 and Nrf2 signaling pathways. Conversely, MCC950 treatment inhibited activation of the NLRP3 signaling pathway, and prevented I/R-induced renal injury, release of cytokines and apoptosis in renal I/R model mice. Sodium hydrosulfide (NaHS) not only alleviated upregulation of NLRP3 protein expression levels, but also relieved renal injury, release of cytokines and cell apoptosis induced by renal I/R in wild-type mice, but not in Nrf2-KO mice. NaHS alleviated NLRP3 inflammasome activation, renal injury, the inflammatory response and cell apoptosis via the Nrf2 signaling pathway in renal I/R model mice. D.A. Spandidos 2021-07 2021-05-17 /pmc/articles/PMC8160482/ /pubmed/34013370 http://dx.doi.org/10.3892/mmr.2021.12157 Text en Copyright: © Su et al. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made. |
spellingShingle | Articles Su, Yonghong Wang, Yaoqi Liu, Min Chen, Hongguang Hydrogen sulfide attenuates renal I/R-induced activation of the inflammatory response and apoptosis via regulating Nrf2-mediated NLRP3 signaling pathway inhibition |
title | Hydrogen sulfide attenuates renal I/R-induced activation of the inflammatory response and apoptosis via regulating Nrf2-mediated NLRP3 signaling pathway inhibition |
title_full | Hydrogen sulfide attenuates renal I/R-induced activation of the inflammatory response and apoptosis via regulating Nrf2-mediated NLRP3 signaling pathway inhibition |
title_fullStr | Hydrogen sulfide attenuates renal I/R-induced activation of the inflammatory response and apoptosis via regulating Nrf2-mediated NLRP3 signaling pathway inhibition |
title_full_unstemmed | Hydrogen sulfide attenuates renal I/R-induced activation of the inflammatory response and apoptosis via regulating Nrf2-mediated NLRP3 signaling pathway inhibition |
title_short | Hydrogen sulfide attenuates renal I/R-induced activation of the inflammatory response and apoptosis via regulating Nrf2-mediated NLRP3 signaling pathway inhibition |
title_sort | hydrogen sulfide attenuates renal i/r-induced activation of the inflammatory response and apoptosis via regulating nrf2-mediated nlrp3 signaling pathway inhibition |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8160482/ https://www.ncbi.nlm.nih.gov/pubmed/34013370 http://dx.doi.org/10.3892/mmr.2021.12157 |
work_keys_str_mv | AT suyonghong hydrogensulfideattenuatesrenalirinducedactivationoftheinflammatoryresponseandapoptosisviaregulatingnrf2mediatednlrp3signalingpathwayinhibition AT wangyaoqi hydrogensulfideattenuatesrenalirinducedactivationoftheinflammatoryresponseandapoptosisviaregulatingnrf2mediatednlrp3signalingpathwayinhibition AT liumin hydrogensulfideattenuatesrenalirinducedactivationoftheinflammatoryresponseandapoptosisviaregulatingnrf2mediatednlrp3signalingpathwayinhibition AT chenhongguang hydrogensulfideattenuatesrenalirinducedactivationoftheinflammatoryresponseandapoptosisviaregulatingnrf2mediatednlrp3signalingpathwayinhibition |