Set 2_R3_raw_gene

Renal
artery stenosis (RAS) engenders
stenotic-kidney ischemia,
dysfunction, and injury, but whether these are
mediated by cellular senescence has not been elucidated. Using INK-ATTAC transgenic
mice,
high-resolution imaging, and unbiased
scRNA-sequencing
of murine kidneys, the authors
identified
cellular senescence as an important mechanism of progressive injury triggered in renal epithelial/stromal cells within
post-stenotic kidneys.
Both P16-specific and
broad quercetin/dasatinib interventions to blunt senescence improved renal function and structure, underscoring its central role in the
pathogenesis of the disease. Furthermore, this mechanism was
conserved in human subjects with RAS. These
observations reveal
new mechanisms that contribute to the pathogenesis of chronic ischemic renal
injury, and support development of senolytic therapy to reduce senescent cell
burden and delay renal injury.