Caspase-3 dependent peritubular capillary dysfunction is pivotal for transition from acute to chronic kidney disease after acute ischemia-reperfusion injury
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12 août 2021
- handle: 10670/1.z71j24
- doi: 10.1152/ajprenal.00690.2020
Mots-clés
Caspase-3 Ischemia-reperfusion injury (IRI) Acute kidney injury (AKI) Microvascular rarefaction FibrosisSujets proches
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Shanshan Lan et al., « Caspase-3 dependent peritubular capillary dysfunction is pivotal for transition from acute to chronic kidney disease after acute ischemia-reperfusion injury », Papyrus : le dépôt institutionnel de l'Université de Montréal, ID : 10.1152/ajprenal.00690.2020
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Résumé
Ischemia-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 dysfunction.