Canonical BMP signaling in tubular cells mediates recovery after acute kidney injury

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Item Type:	Article
Title:	Canonical BMP signaling in tubular cells mediates recovery after acute kidney injury
Creators Name:	Vigolo, E., Markó, L., Hinze, C., Müller, D.N., Schmidt-Ullrich, R. and Schmidt-Ott, K.M.
Abstract:	Bone morphogenetic protein (BMP) signaling has been shown to modulate the development of renal fibrosis in animal models of kidney injury, but the downstream mediators are incompletely understood. In wild-type mice, canonical BMP signaling mediated by SMAD1/5/8 transcription factors was constitutively active in healthy renal tubules, transiently down-regulated after ischemia reperfusion injury (IRI), and reactivated during successful tubular regeneration. We then induced IRI in mice with a tubular-specific BMP receptor 1A (BMPR1A) deletion. These mice failed to reactivate SMAD1/5/8 signaling in the post-ischemic phase and developed renal fibrosis after injury. Using unbiased genomic analyses, we identified three genes encoding inhibitor of DNA-binding (ID) proteins (Id1, Id2, and Id4) as key targets of BMPR1A-SMAD1/5/8 signaling. BMPR1A-deficient mice failed to re-induce these targets following IRI. Instead, BMPR1A-deficiency resulted in activation of pro-fibrotic signaling proteins that are normally repressed by ID proteins, namely, p38 mitogen-activated protein kinase and cell cycle inhibitor p27. These data indicate that the post-ischemic activation of canonical BMP signaling acts endogenously to repress pro-fibrotic signaling in tubular cells and may help to prevent the progression of acute kidney injury to chronic kidney disease.
Keywords:	Fibrosis, Ischemia Reperfusion Injury, Renal Tubular Epithelial Cells, SMAD Transcription Factors, Animals, Mice
Source:	Kidney International
ISSN:	0085-2538
Publisher:	Elsevier
Volume:	95
Number:	1
Page Range:	108-122
Date:	January 2019
Official Publication:	https://doi.org/10.1016/j.kint.2018.08.028
PubMed:	View item in PubMed

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