This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Matsushita, M. Articles by Hirata, Y. Search for Related Content PubMed PubMed Citation Articles by Matsushita, M. Articles by Hirata, Y. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Hazardous Substances DB CALCIUM COMPOUNDS CALCIUM, ELEMENTAL

Urotensin II is an Autocrine/Paracrine Growth Factor for the Porcine Renal Epithelial Cell Line, LLCPK1

Department of Clinical and Molecular Endocrinology (M.M., M.S., N.F., N.O., T.Y., Y.H.), Tokyo Medical and Dental University Graduate School, Tokyo, 113-8519, Japan; and Second Department of Internal Medicine (N.T.), University of Ryukyus, Okinawa 903-0215, Japan

Address all correspondence and requests for reprints to: Yukio Hirata, M.D., Department of Clinical and Molecular Endocrinology, Tokyo Medical and Dental University Graduate School, Yushima 1-5-45, Bunkyo-ku, Tokyo 113-8519, Japan. E-mail: yhirata.cme{at}tmd.ac.jp.

Urotensin-II (UII), a cyclic dodecapeptide with potent cardiovascular effects, has recently been shown to be abundantly expressed in the human kidney and excreted in human urine. To investigate whether UII acts as an autocrine/paracrine growth factor for renal epithelial cells, we have studied the effects of human UII (hUII) on DNA synthesis, cytosolic free Ca²⁺ concentration ([Ca²⁺]_i), ERK activation, and protooncogene (c-myc) expression in a porcine renal epithelial cell line (LLCPK1). hUII stimulated [³H]thymidine uptake into quiescent cells in a dose-dependent manner (10^-9 to 10^-7 M); this effect was inhibited by a protein kinase C inhibitor (GF109203X), a MAPK kinase inhibitor (PD98059), and a calcium channel blocker (nicardipine). Neither phosphatidyl inositol-3 kinase inhibitors (LY294002, wortmannin) nor p38 kinase inhibitor (SB203580) affected the hUII-induced DNA syntheses. hUII rapidly (within 5 min) and dose-dependently (10^-9 to 10^-7 M) increased [Ca²⁺]_i in fura-2-loaded cells. hUII also caused a rapid and transient activation of ERK1/2 and induction of c-myc. LLCPK1 cells expressed UII mRNA and its receptor GPR14 mRNA, as determined by RT-PCR, and released UII-like immunoreactivity into media. Neutralization of endogenous UII by anti-hUII antibody, but not nonimmune serum, significantly suppressed DNA synthesis. These data suggest that hUII is an autocrine/paracrine growth factor for renal epithelial cells via activation of both protein kinase C and ERK1/2 pathways as well as Ca²⁺ influx via voltage-dependent Ca²⁺ channels.

This article has been cited by other articles:

				J.-C. Liu, C.-H. Chen, J.-J. Chen, and T.-H. Cheng Urotensin II Induces Rat Cardiomyocyte Hypertrophy via the Transient Oxidization of Src Homology 2-Containing Tyrosine Phosphatase and Transactivation of Epidermal Growth Factor Receptor Mol. Pharmacol., December 1, 2009; 76(6): 1186 - 1195. [Abstract] [Full Text] [PDF]

				L. Tian, C. Li, J. Qi, P. Fu, X. Yu, X. Li, and L. Cai Diabetes-induced upregulation of urotensin II and its receptor plays an important role in TGF-{beta}1-mediated renal fibrosis and dysfunction Am J Physiol Endocrinol Metab, November 1, 2008; 295(5): E1234 - E1242. [Abstract] [Full Text] [PDF]

				A. E S Abdel-Razik, E. J Forty, R. J Balment, and N. Ashton Renal haemodynamic and tubular actions of urotensin II in the rat J. Endocrinol., September 1, 2008; 198(3): 617 - 624. [Abstract] [Full Text] [PDF]

				A. Mosenkis, T. M. Danoff, N. Aiyar, J. Bazeley, and R. R. Townsend Human Urotensin II in the plasma of anephric subjects Nephrol. Dial. Transplant., April 1, 2007; 22(4): 1269 - 1270. [Full Text] [PDF]

				T. Watanabe, T. Suguro, T. Kanome, Y.-i. Sakamoto, S. Kodate, T. Hagiwara, S. Hongo, T. Hirano, M. Adachi, and A. Miyazaki Human Urotensin II Accelerates Foam Cell Formation in Human Monocyte-Derived Macrophages Hypertension, October 1, 2005; 46(4): 738 - 744. [Abstract] [Full Text] [PDF]

				T. Djordjevic, R. S. BelAiba, S. Bonello, J. Pfeilschifter, J. Hess, and A. Gorlach Human Urotensin II Is a Novel Activator of NADPH Oxidase in Human Pulmonary Artery Smooth Muscle Cells Arterioscler Thromb Vasc Biol, March 1, 2005; 25(3): 519 - 525. [Abstract] [Full Text] [PDF]