Regulation of Embryonic Kidney Branching Morphogenesis and Glomerular Development by KISS1 Receptor (Gpr54) Through NFAT2- and Sp1-mediated Bmp7 Expression

Overview

Journal J Biol Chem

Specialty Biochemistry

Date 2010 Apr 9

PMID 20375015

Citations 17

Authors

Tingfang Yi

Kunrong Tan

Sung-Gook Cho

Ying Wang

Jian Luo

Wenzheng Zhang

Dali Li

Mingyao Liu

Affiliations

Soon will be listed here.

Abstract

G-protein-coupled receptor 54 (Gpr54, KISS1 receptor) plays critical roles in puberty regulation, tumor metastasis suppression, and vasoconstriction. Bone morphogenetic protein-7 (Bmp7) is required for kidney organogenesis. However, whether Gpr54 is involved in embryonic kidney development and how Bmp7 expression is regulated in the kidney are largely unknown. Here we report that Gpr54 deletion leads to kidney branching morphogenesis and glomerular development retardation in embryonic kidneys in vivo and in explanted kidneys in vitro. Gpr54 inactivation results in a high risk of low glomerular number in adult kidneys. Gpr54 is expressed in condensed mesenchyme at E12.5 and epithelial cells of proximal and distal tubules and collecting ducts at E17.5 and P0 mouse kidney. Deletion of Gpr54 decreases Bmp7 expression and Smad1 phosphorylation in the developing kidney. Using chromatin immunoprecipitation and luciferase assays, we demonstrate that Gpr54 regulates NFAT2- and Sp1-mediated Bmp7 transcription. Furthermore, we show that NFAT2 cooperates with Sp1 to promote Bmp7 transcription activation. Together, these data suggest that Gpr54 regulates Bmp7 expression through NFAT2 and Sp1 and plays an important role in embryonic kidney branching morphogenesis and glomerular development.

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References

Zhao C, Meng A . Sp1-like transcription factors are regulators of embryonic development in vertebrates. Dev Growth Differ. 2005; 47(4):201-11. DOI: 10.1111/j.1440-169X.2005.00797.x. View

Cebrian C, Borodo K, Charles N, Herzlinger D . Morphometric index of the developing murine kidney. Dev Dyn. 2004; 231(3):601-8. DOI: 10.1002/dvdy.20143. View

Yellaturu C, Ghosh S, Rao R, Jennings L, Hassid A, Rao G . A potential role for nuclear factor of activated T-cells in receptor tyrosine kinase and G-protein-coupled receptor agonist-induced cell proliferation. Biochem J. 2002; 368(Pt 1):183-90. PMC: 1222985. DOI: 10.1042/BJ20020347. View

Gurgel Teles M, Bianco S, Brito V, Trarbach E, Kuohung W, Xu S . A GPR54-activating mutation in a patient with central precocious puberty. N Engl J Med. 2008; 358(7):709-15. PMC: 2859966. DOI: 10.1056/NEJMoa073443. View

Navarro V, Castellano J, Fernandez-Fernandez R, Barreiro M, Roa J, Sanchez-Criado J . Developmental and hormonally regulated messenger ribonucleic acid expression of KiSS-1 and its putative receptor, GPR54, in rat hypothalamus and potent luteinizing hormone-releasing activity of KiSS-1 peptide. Endocrinology. 2004; 145(10):4565-74. DOI: 10.1210/en.2004-0413. View

Ikeguchi M, Yamaguchi K, Kaibara N . Clinical significance of the loss of KiSS-1 and orphan G-protein-coupled receptor (hOT7T175) gene expression in esophageal squamous cell carcinoma. Clin Cancer Res. 2004; 10(4):1379-83. DOI: 10.1158/1078-0432.ccr-1519-02. View

Nicolle G, Comperat E, Nicolaiew N, Cancel-Tassin G, Cussenot O . Metastin (KISS-1) and metastin-coupled receptor (GPR54) expression in transitional cell carcinoma of the bladder. Ann Oncol. 2006; 18(3):605-7. DOI: 10.1093/annonc/mdl421. View

Mitu G, Wang S, Hirschberg R . BMP7 is a podocyte survival factor and rescues podocytes from diabetic injury. Am J Physiol Renal Physiol. 2007; 293(5):F1641-8. DOI: 10.1152/ajprenal.00179.2007. View

Cain J, Hartwig S, Bertram J, Rosenblum N . Bone morphogenetic protein signaling in the developing kidney: present and future. Differentiation. 2008; 76(8):831-42. DOI: 10.1111/j.1432-0436.2008.00265.x. View

10.

Ohta S, Lai E, Pang A, Brouwers F, Chan W, Eisenhofer G . Downregulation of metastasis suppressor genes in malignant pheochromocytoma. Int J Cancer. 2004; 114(1):139-43. DOI: 10.1002/ijc.20670. View

11.

Jiang T, Zhang S, Lin B, Meng L, Gao H . [Expression and clinical significance of KISS-1 and GPR54 mRNA in endometrial carcinoma]. Zhonghua Zhong Liu Za Zhi. 2005; 27(4):229-31. View

12.

Liu X, Lee K, Herbison A . Kisspeptin excites gonadotropin-releasing hormone neurons through a phospholipase C/calcium-dependent pathway regulating multiple ion channels. Endocrinology. 2008; 149(9):4605-14. PMC: 6116891. DOI: 10.1210/en.2008-0321. View

13.

Sugimoto T, Haneda M, Sawano H, Isshiki K, Maeda S, Koya D . Endothelin-1 induces cyclooxygenase-2 expression via nuclear factor of activated T-cell transcription factor in glomerular mesangial cells. J Am Soc Nephrol. 2001; 12(7):1359-1368. DOI: 10.1681/ASN.V1271359. View

14.

Paralkar V, Grasser W, Mansolf A, Baumann A, Owen T, Smock S . Regulation of BMP-7 expression by retinoic acid and prostaglandin E(2). J Cell Physiol. 2002; 190(2):207-17. DOI: 10.1002/jcp.10048. View

15.

Seminara S, Messager S, Chatzidaki E, Thresher R, Acierno Jr J, Shagoury J . The GPR54 gene as a regulator of puberty. N Engl J Med. 2003; 349(17):1614-27. DOI: 10.1056/NEJMoa035322. View

16.

dAnglemont de Tassigny X, Fagg L, Carlton M, Colledge W . Kisspeptin can stimulate gonadotropin-releasing hormone (GnRH) release by a direct action at GnRH nerve terminals. Endocrinology. 2008; 149(8):3926-32. PMC: 2488229. DOI: 10.1210/en.2007-1487. View

17.

Zhang C, Roepke T, Kelly M, Ronnekleiv O . Kisspeptin depolarizes gonadotropin-releasing hormone neurons through activation of TRPC-like cationic channels. J Neurosci. 2008; 28(17):4423-34. PMC: 6670958. DOI: 10.1523/JNEUROSCI.5352-07.2008. View

18.

Qiao J, Sakurai H, Nigam S . Branching morphogenesis independent of mesenchymal-epithelial contact in the developing kidney. Proc Natl Acad Sci U S A. 1999; 96(13):7330-5. PMC: 22085. DOI: 10.1073/pnas.96.13.7330. View

19.

Adams D, Karolak M, Robertson E, Oxburgh L . Control of kidney, eye and limb expression of Bmp7 by an enhancer element highly conserved between species. Dev Biol. 2007; 311(2):679-90. PMC: 2394512. DOI: 10.1016/j.ydbio.2007.08.036. View

20.

Funes S, Hedrick J, Vassileva G, Markowitz L, Abbondanzo S, Golovko A . The KiSS-1 receptor GPR54 is essential for the development of the murine reproductive system. Biochem Biophys Res Commun. 2003; 312(4):1357-63. DOI: 10.1016/j.bbrc.2003.11.066. View