{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T04:11:42Z","timestamp":1792469502300,"version":"4.5.0"},"reference-count":22,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"7","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JASN"],"published-print":{"date-parts":[[2018,7]]},"abstract":"\n Background<\/jats:bold>\n Ischemia-reperfusion injury (IRI) is a major risk factor for chronic renal failure. Here, we characterize the different modes of programmed cell death in the tubular and microvascular compartments during the various stages of IRI-induced AKI, and their relative importance to renal fibrogenesis.\n <\/jats:p>\n \n Methods<\/jats:bold>\n We performed unilateral renal artery clamping for 30 minutes and contralateral nephrectomy in wild-type mice (C57BL\/6) or caspase-3\n \u2212\/\u2212<\/jats:sup>\n mice.\n <\/jats:p>\n \n Results<\/jats:bold>\n Compared with their wild-type counterparts, caspase-3\n \u2212\/\u2212<\/jats:sup>\n mice in the early stage of AKI had high urine cystatin C levels, tubular injury scores, and serum creatinine levels. Electron microscopy revealed evidence of tubular epithelial cell necrosis in caspase-3\n \u2212\/\u2212<\/jats:sup>\n mice, and immunohistochemistry showed upregulation of the necroptosis marker receptor-interacting serine\/threonine-protein kinase 3 (RIPK3) in renal cortical sections. Western blot analysis further demonstrated enhanced levels of phosphorylated RIPK3 in the kidneys of caspase-3\n \u2212\/\u2212<\/jats:sup>\n mice. In contrast, caspase-3\n \u2212\/\u2212<\/jats:sup>\n mice had less microvascular congestion and activation in the early and extension phases of AKI. In the long term (3 weeks after IRI), caspase-3\n \u2212\/\u2212<\/jats:sup>\n mice had reduced microvascular rarefaction and renal fibrosis, as well as decreased expression of\n \u03b1<\/jats:italic>\n -smooth muscle actin and reduced collagen deposition within peritubular capillaries. Moreover, caspase-3\n \u2212\/\u2212<\/jats:sup>\n mice exhibited signs of reduced tubular ischemia, including lower tubular expression of hypoxia-inducible factor-1\n \u03b1<\/jats:italic>\n and improved tubular injury scores.\n <\/jats:p>\n \n Conclusions<\/jats:bold>\n These results establish the pivotal importance of caspase-3 in regulating microvascular endothelial cell apoptosis and renal fibrosis after IRI. These findings also demonstrate the predominant role of microvascular over tubular injury as a driver of progressive renal damage and fibrosis after IRI.\n <\/jats:p>","DOI":"10.1681\/asn.2017050581","type":"journal-article","created":{"date-parts":[[2018,6,20]],"date-time":"2018-06-20T10:26:25Z","timestamp":1529490385000},"page":"1900-1916","source":"Crossref","is-referenced-by-count":149,"title":["Caspase-3 Is a Pivotal Regulator of Microvascular Rarefaction and Renal Fibrosis after Ischemia-Reperfusion Injury"],"prefix":"10.1681","volume":"29","author":[{"given":"Bing","family":"Yang","sequence":"first","affiliation":[{"name":"Research Centre, Centre hospitalier de l\u2019Universit\u00e9 de Montr\u00e9al, Montreal, Quebec, Canada;"},{"name":"Canadian National Transplant Research Program, Edmonton, Alberta, Canada;"},{"name":"Universit\u00e9 de Montr\u00e9al, Montreal, Quebec, Canada;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shanshan","family":"Lan","sequence":"additional","affiliation":[{"name":"Research Centre, Centre hospitalier de l\u2019Universit\u00e9 de Montr\u00e9al, Montreal, Quebec, Canada;"},{"name":"Canadian National Transplant Research Program, Edmonton, Alberta, Canada;"},{"name":"Universit\u00e9 de Montr\u00e9al, Montreal, Quebec, Canada;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M\u00e9lanie","family":"Dieud\u00e9","sequence":"additional","affiliation":[{"name":"Research Centre, Centre hospitalier de l\u2019Universit\u00e9 de Montr\u00e9al, Montreal, Quebec, Canada;"},{"name":"Canadian National Transplant Research Program, Edmonton, Alberta, Canada;"},{"name":"Universit\u00e9 de Montr\u00e9al, Montreal, Quebec, Canada;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean-Paul","family":"Sabo-Vatasescu","sequence":"additional","affiliation":[{"name":"Research Centre, Centre hospitalier de l\u2019Universit\u00e9 de Montr\u00e9al, Montreal, Quebec, Canada;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annie","family":"Karakeussian-Rimbaud","sequence":"additional","affiliation":[{"name":"Research Centre, Centre hospitalier de l\u2019Universit\u00e9 de Montr\u00e9al, Montreal, Quebec, Canada;"},{"name":"Canadian National Transplant Research Program, Edmonton, Alberta, Canada;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julie","family":"Turgeon","sequence":"additional","affiliation":[{"name":"Research Centre, Centre hospitalier de l\u2019Universit\u00e9 de Montr\u00e9al, Montreal, Quebec, Canada;"},{"name":"Canadian National Transplant Research Program, Edmonton, Alberta, Canada;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shijie","family":"Qi","sequence":"additional","affiliation":[{"name":"Research Centre, Centre hospitalier de l\u2019Universit\u00e9 de Montr\u00e9al, Montreal, Quebec, Canada;"},{"name":"Canadian National Transplant Research Program, Edmonton, Alberta, Canada;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lakshman","family":"Gunaratnam","sequence":"additional","affiliation":[{"name":"Canadian National Transplant Research Program, Edmonton, Alberta, Canada;"},{"name":"London Health Sciences Centre, Schulich School of Medicine and Dentistry, The University of Western Ontario, London, Ontario, Canada; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalie","family":"Patey","sequence":"additional","affiliation":[{"name":"Research Centre, Centre hospitalier de l\u2019Universit\u00e9 de Montr\u00e9al, Montreal, Quebec, Canada;"},{"name":"Canadian National Transplant Research Program, Edmonton, Alberta, Canada;"},{"name":"Universit\u00e9 de Montr\u00e9al, Montreal, Quebec, Canada;"},{"name":"Department of Pathology, Centre hospitalier universitaire Sainte-Justine, Universit\u00e9 de Montr\u00e9al, Montreal, Quebec, 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