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Localization of O₂‑sensing ADO‑RGS pathway components in mouse and human kidneys under normoxia, hypoxia and renal fibrosis

Pflügers Archiv

Published online on

Abstract

{"__content__"=>"\n Graphical Abstract\n \n ", "p"=>[{"__content__"=>"Cellular adaptation to hypoxia is essential for maintaining function and survival. While most hypoxic responss are mediated by hypoxia‑inducible factor signaling, the oxygen‑dependent ADO–RGS (2‑Aminoethanethiol-Dioxygenase—Regulator of G‑Protein Signaling) pathway has recently been implicated in oxygen‑sensitive regulation of G‑protein signaling. The kidneys are particularly vulnerable to hypoxia, a major contributor to chronic kidney disease. Because a systematic characterization of ADO and its RGS substrates across renal cell types is lacking, this study examined their spatial expression patterns in mouse and human kidneys under (patho)physiological conditions. and , , and expression was mapped in mouse kidney sections under normoxic, hypoxic, and fibrotic conditions using RNAscope™, complemented by RT‑qPCR. Mouse data were compared with - expression patterns in human biopsies. expression was uniform across renal regions, cell types, and conditions. Besides its baseline presence in vascular cells, showed strong induction in cortical and outer medullary fibroblasts during anemia. It was also upregulated in fibroblasts and proximal tubules within fibrotic lesions. was highly expressed in vascular structures and demonstrated hypoxia‑induced upregulation in medullary fibroblasts and , with moderate induction under fibrotic conditions. Tubular epithelial expression also occurred during fibrosis. was mostly expressed in interstitial cells in fibrotic kidneys. Human kidney-disease biopsies also displayed distinct and expression patterns. Overall, these findings suggest that while ADO is consistently present, the functional impact of ADO–RGS signaling may be driven by dynamic, cell‑type‑specific regulation of RGS genes during acute and chronic hypoxic stress.", "i"=>[{"__content__"=>"Ado"}, {"__content__"=>"Rgs4"}, {"__content__"=>"Rgs5"}, {"__content__"=>"Rgs16"}, {"__content__"=>"ADO"}, {"__content__"=>"RGS"}, {"__content__"=>"Ado"}, {"__content__"=>"Rgs4"}, {"__content__"=>"Rgs5"}, {"__content__"=>"vasa recta"}, {"__content__"=>"Rgs16"}, {"__content__"=>"Pdgfrb⁺"}, {"__content__"=>"RGS4"}, {"__content__"=>"RGS5"}]}, {}]}