Indian Hedgehog release from TNF-activated renal epithelia drives local and remote organ fibrosis.

ABSTRACT: Progressive fibrosis is a feature of aging and chronic tissue injury in multiple organs, including the kidney and heart. Glioma-associated oncogene 1 expressing (Gli1⁺) cells are a major source of activated fibroblasts in multiple organs, but the links between injury, inflammation, and Gli1⁺ cell expansion and tissue fibrosis remain incompletely understood. We demonstrated that leukocyte-derived tumor necrosis factor (TNF) promoted Gli1⁺ cell proliferation and cardiorenal fibrosis through induction and release of Indian Hedgehog (IHH) from renal epithelial cells. Using single-cell-resolution transcriptomic analysis, we identified an "inflammatory" proximal tubular epithelial (iPT) population contributing to TNF- and nuclear factor κB (NF-κB)-induced IHH pro

SUBMITTER: O'Sullivan ED 

PROVIDER: S-EPMC11977576 | biostudies-literature | 2023 May

REPOSITORIES: biostudies-literature