Notch-3 receptor activation drives inflammation and fibrosis following tubulointerstitial kidney injury.

摘要: Kidney diseases impart a vast burden on affected individuals and the overall health care system. Progressive loss of renal parenchymal cells functional decline following injury are often observed. Notch-1 -2 receptors crucially involved in nephron development contribute to inflammatory kidney diseases. We specifically determined participation receptor Notch-3 tubulointerstitial responses. Here we show by heat map analyses that transcripts up-regulated human A similar response was corroborated with TGF-β exposure vitro. The murine unilateral ureteral obstruction (UUO) model mirrors hallmarks damage. subset tubular interstitial demonstrated expression diseased animals. hypothesized relevance for chemotactic response. To address this question, animals genetic ablation were analysed UUO. As result, found Notch-3-deficient protected from cell significantly reduced collagen deposition. Monocytic infiltration retarded, likely due abrogated chemokine synthesis. set up mimics enhanced activation. pro-mitogenic seen activated signalling fibroblasts. In conclusion, fulfils non-redundant roles inflamed may not be replaced other Notch family members. Thus, specific blockade suitable as therapeutic option delay progression disease.