TY - JOUR
T1 - Prokineticin receptor 1 is required for mesenchymal-epithelial transition in kidney development
AU - Arora, Himanshu
AU - Boulberdaa, Mounia
AU - Qureshi, Rehana
AU - Bitirim, Verda
AU - Messadeq, Nadia
AU - Dolle, Pascal
AU - Nebigil, Canan G.
N1 - Publisher Copyright:
© FASEB.
PY - 2016/8
Y1 - 2016/8
N2 - 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 theGata5 (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 PKRG52/2 mice are manifested in the adult stage as renal atrophy with glomerular defects, nephropathy, and uremia.PKR1Wt12/2 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 crucialmodifier 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.
AB - 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 theGata5 (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 PKRG52/2 mice are manifested in the adult stage as renal atrophy with glomerular defects, nephropathy, and uremia.PKR1Wt12/2 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 crucialmodifier 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.
KW - Genetically altered mice
KW - Receptor pharmacology
KW - Renal physiology/pathophysiology
UR - http://www.scopus.com/inward/record.url?scp=84980354905&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84980354905&partnerID=8YFLogxK
U2 - 10.1096/fj.201600181R
DO - 10.1096/fj.201600181R
M3 - Article
C2 - 27084889
AN - SCOPUS:84980354905
VL - 30
SP - 2733
EP - 2740
JO - FASEB Journal
JF - FASEB Journal
SN - 0892-6638
IS - 8
ER -
