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dc.contributor.authorLan, Shanshan
dc.contributor.authorYang, Bing
dc.contributor.authorMigneault, Francis
dc.contributor.authorTurgeon, Julie
dc.contributor.authorBourgault, Maude
dc.contributor.authorDieudé, Mélanie
dc.contributor.authorCardinal, Héloïse
dc.contributor.authorHickey, Michael
dc.contributor.authorPatey, Natacha
dc.contributor.authorHébert, Marie-Josée
dc.publisherAmerican Physiological Societyfr
dc.subjectIschemia-reperfusion injury (IRI)fr
dc.subjectAcute kidney injury (AKI)fr
dc.subjectMicrovascular rarefactionfr
dc.titleCaspase-3 dependent peritubular capillary dysfunction is pivotal for transition from acute to chronic kidney disease after acute ischemia-reperfusion injuryfr
dc.contributor.affiliationUniversité de Montréal. Faculté de médecine. Département de médecinefr
dcterms.abstractIschemia-reperfusion injury (IRI) is a major risk factor for chronic renal failure. Caspase-3, an effector responsible for apoptosis execution, is activated within peritubular capillary (PTC) in the early stage of IRI-induced acute kidney injury (AKI). Recently, we showed that caspase-3-dependent microvascular rarefaction plays a key role in fibrosis development after mild renal IRI. Here, we further characterize the role of caspase-3 in microvascular dysfunction and progressive renal failure in both mild and severe AKI, by performing unilateral renal artery clamping for 30/60 minutes with contralateral nephrectomy in wild-type (C57BL/6) or caspase-3-/- mice. In both forms of AKI, caspase-3-/- mice showed better long-term outcomes in spite of worse initial tubular injury. After 3 weeks, they showed reduced PTC injury, decreased PTC collagen deposition and α-SMA expression, and lower tubular injury scores when compared to wild-type animals. Caspase-3-/- mice with severe IRI also showed better preservation of long-term renal function. Intra-vital imaging and micro Computed Tomography (microCT) revealed preserved PTCs permeability and better terminal capillary density in caspase-3-/- mice. Collectively, these results demonstrate the pivotal importance of caspase-3 in regulating long-term renal function after IRI and establish the predominant role of PTCs dysfunction as a major contributor to progressive renal
UdeM.ReferenceFournieParDeposantDOI: 10.1152/ajprenal.00690.2020fr
UdeM.VersionRioxxVersion acceptée / Accepted Manuscriptfr
oaire.citationTitleAmerican journal of physiology : renal physiologyfr

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