Key result
Depletion of mast cells prior to renal ischemia-reperfusion injury improved renal function and reduced subsequent fibrosis, whereas ablation after the acute phase had no impact.
Why the study?
Does conditional ablation of mast cells prevent renal damage and fibrosis in a mouse model of renal ischemia-reperfusion injury?
Does conditional ablation of mast cells prevent renal damage and fibrosis in a mouse model of renal ischemia-reperfusion injury?
Mast cell depletion prior to acute renal ischemia-reperfusion injury attenuates subsequent chronic fibrosis and organ atrophy, highlighting a potential therapeutic target in the early injury phase.
Early mast cell depletion may limit post-IRI fibrosis in mice; leaves open translation to human AKI.
Ischemia-reperfusion injury (IRI) is an important cause of acute kidney injury that can lead to end-stage renal failure. Although the ensuing inflammatory response can restore homeostasis, a consecutive maladaptive repair and persistent inflammation represent important risk factors for postischemic chronic kidney disease development. In this study, we investigated the role of mast cells in both the early and late phases of the inflammatory response in experimental models of acute and chronic renal IRI using our recently developed mouse model that allows conditional ablation of mast cells. Depletion of mast cells prior to IRI resulted in improved renal function due to diminished local inflammatory cytokine/chemokine levels and neutrophil recruitment to the kidneys after the acute injury phase (48 h post-IRI). Furthermore, although not completely protected, mast cell-depleted mice displayed less organ atrophy and fibrosis than did wild-type mice during the chronic phases (2 and 6 wk post-IRI) of disease development. Conversely, mast cell ablation after the acute phase of IRI had no impact on organ atrophy, tubular necrosis, or fibrosis. Thus, our results suggest a deleterious role of mast cells during the acute inflammatory phase of IRI promoting subsequent fibrosis development, but not during the chronic phase of the disease.
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Danelli et al. (2017) studied Renal ischemia-reperfusion injury (IRI). Mast cell depletion vs. Wild-type mice was evaluated on Renal function, local inflammatory cytokine/chemokine levels, neutrophil recruitment, organ atrophy, and fibrosis. Depletion of mast cells prior to renal ischemia-reperfusion injury improved renal function and reduced subsequent fibrosis, whereas ablation after the acute phase had no impact.
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