{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T23:13:25Z","timestamp":1790378005001,"version":"4.1.0"},"reference-count":32,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2022,3,1]],"date-time":"2022-03-01T00:00:00Z","timestamp":1646092800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"name":"Technology Project of Guangdong Province","award":["2015B020211006"],"award-info":[{"award-number":["2015B020211006"]}]},{"name":"Technology Project of Guangdong Province","award":["201604020137]"],"award-info":[{"award-number":["201604020137]"]}]},{"name":"Technology Project of Guangdong Province","award":["201604020137"],"award-info":[{"award-number":["201604020137"]}]},{"name":"Shenzhen Longhua District Science and Technology Innovation","award":["2020036"],"award-info":[{"award-number":["2020036"]}]},{"name":"Shenzhen Longhua District Science and Technology Innovation","award":["2017032"],"award-info":[{"award-number":["2017032"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,3,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Objective<\/jats:title>\n                  <jats:p>This study explores the potential role of a highly selective caspase-1 inhibitor, VX-765, on extracellular matrix (ECM) accumulation and inflammation in diabetic nephropathy (DN) and the underlying mechanisms.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>DN rats, induced via high-fat diet\/streptozotocin, were used to assess the effects of VX-765. Parallel experiments were carried out on rat mesangial cell line HBZY-1 exposed to high glucose (HG) to reveal the molecular mechanism of VX-765 in preventing DN. Survival analysis, biochemical parameters and renal oxidative stress of rats were observed, and Western blotting and immunofluorescence were evaluated. In vitro, Nicotinamide adenine dinucleotide phosphate (NADPH) oxidases (NOX)1 silencing by RNA interference and quantitative real-time PCR (qPCR) assays were conducted in HBZY-1 cells exposed to HG levels.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Key findings<\/jats:title>\n                  <jats:p>In vivo, VX-765 significantly reduced the increase in urine albumin excretion and ECM accumulation. The phosphorylation of nuclear factor kappa-B (NF-\u03baB) and the expression of pro-inflammatory cytokines IL-1\u03b2, IL-6 and tumor necrosis factor (TNF)-\u03b1 were significantly down-regulated. Furthermore, the generation of reactive oxygen species (ROS), phosphorylation of NF-\u03baB and the expression of the NOX1 gene or protein were significantly decreased in HBZY-1 with VX-765 (5 \u03bcM) treatment in vitro.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Our results demonstrated that VX-765 exerts favourable effects on DN via the simultaneous alleviation of systemic metabolic syndrome and down-regulating the renal NOX1\/ROS\/NF-\u03baB pathway, suggesting that it has therapeutic potential for DN.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/jpp\/rgab112","type":"journal-article","created":{"date-parts":[[2021,7,15]],"date-time":"2021-07-15T11:17:09Z","timestamp":1626347829000},"page":"377-386","source":"Crossref","is-referenced-by-count":19,"title":["VX-765 ameliorates inflammation and extracellular matrix accumulation by inhibiting the NOX1\/ROS\/NF-\u03baB pathway in diabetic nephropathy"],"prefix":"10.1093","volume":"74","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4325-9907","authenticated-orcid":false,"given":"Xiaokang","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Pharmacy, Shenzhen Longhua District Central Hospital, The Affiliated Central Hospital of Shenzhen Longhua District, Guangdong Medical University , Shenzhen ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tiesong","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Shenzhen Longhua District Central Hospital, The Affiliated Central Hospital of Shenzhen Longhua District, Guangdong Medical University , Shenzhen ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongyan","family":"Ma","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Shenzhen Longhua District Central Hospital, The Affiliated Central Hospital of Shenzhen Longhua District, Guangdong Medical University , Shenzhen ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoling","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Shenzhen Longhua District Central Hospital, The Affiliated Central Hospital of Shenzhen Longhua District, Guangdong Medical University , Shenzhen ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaiyuan","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Shenzhen Longhua District Central Hospital, The Affiliated Central Hospital of Shenzhen Longhua District, Guangdong Medical University , Shenzhen ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunxiao","family":"Ye","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Shenzhen Hospital of Southern Medical University , Shenzhen 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