Details

Autor(en) / Beteiligte

• Arora, Himanshu
• Boulberdaa, Mounia
• Qureshi, Rehana
• Bitirim, Verda
• Messadeq, Nadia
• Dolle, Pascal
• Nebigil, Canan G.

Titel

Prokineticin receptor 1 is required for mesenchymal‐epithelial transition in kidney development

Ist Teil von

• The FASEB journal, 2016-08, Vol.30 (8), p.2733-2740

Ort / Verlag

United States: Federation of American Societies for Experimental Biology

Erscheinungsjahr

2016

Link zum Volltext

Quelle

Wiley Blackwell Single Titles

Beschreibungen/Notizen

• ABSTRACT Identification of factors regulating renal development is important to understand the pathogenesis of congenital kidney diseases. Little is known about the molecular mechanism of renal development and functions triggered by the angiogenic hormone prokineticin‐2 and its receptor, PKR1. Utilizing the Gata5 (G5)‐Cre and Wilms tumor 1 (Wt1)GFPcre transgenic lines, we generated mutant mice with targeted PKR1 gene disruptions in nephron progenitors. These mutant mice exhibited partial embryonic and postnatal lethality. Kidney developmental defects in PKRG5‐/‐ mice are manifested in the adult stage as renal atrophy with glomerular defects, nephropathy, and uremia. PKR1Wf1‐/‐ embryos exhibit hypoplastic kidneys with premature glomeruli and necrotic nephrons as a result of impaired proliferation and increased apoptosis in Wt1+ renal mesenchymal cells. PKR1 regulates renal mesenchymal‐epithelial transition (MET) that is involved in formation of renal progenitors, regulating glomerulogenesis toward forming nephrons during kidney development. In the isolated embryonic Wt1+ renal cells, overexpression or activation of PKR1 promotes MET defined by the transition from elongated cell to octagonal cell morphology, and alteration of the expression of MET markers via activating NFATc3 signaling. Together, these results establish PKR1 via NFATc3 as a crucial modifier of MET processing to the development of nephron. Our study should facilitate new therapeutic opportunities in human renal disorders.—Arora, H., Boulberdaa, M., Qureshi, R., Bitirim, V., Messadeq, N., Dolle, P., Nebigil, C. G. Prokineticin receptor 1 is required for mesenchymal‐epithelial transition in kidney development. FASEB J. 30, 2733‐2740 (2016). www.fasebj.org