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Diabetes-induced upregulation of urotensin II and its receptor plays an important role in TGF-beta1-mediated renal fibrosis and dysfunction.
Am J Physiol Endocrinol Metab. 2008 Nov; 295(5):E1234-42.AJ

Abstract

Urotensin II (UII) was identified as the ligand for a novel G protein-coupled receptor, GPR14. UII was found not only to have a potent vasoconstrictive action but also to have profibrotic effects in the heart. The present study was to define whether UII and GPR14 also play important roles in diabetes-induced renal fibrosis and dysfunction. Diabetic rats were induced using streptozotocin, and the rat proximal tubular epithelial cells (NRK-52E) were used for the in vitro mechanism study. Results showed that expression of UII and GPR14 was significantly upregulated at both mRNA and protein levels in the diabetic kidneys compared with controls. The upregulated expressions of UII and GPR14 in the kidney were accompanied by significant increases in the renal profibrotic factor transforming growth factor (TGF)-beta1 expression, the renal extracellular matrix (fibronectin and collagen IV) accumulation, and the renal dysfunction (increases in urinal N-acetyl-beta-d-glucosaminidase content, 24-h urinary retinol-binding protein excretion rate, and decrease in creatinine clearance rate). Exposure of NRK-52E cells to 10(-8) mol/l UII for 48 h caused a significant increase of TGF-beta1, but not ANG II, production that was GPR14- and calcium-dependent, since GPR14 small-interfering RNA and calcium channel blocker nimodipine or calcium chelator EDTA all could abolish the induction of TGF- beta1 by UII. Furthermore, exposure of NRK-52E cells to TGF-beta1 or ANG II also increased UII and GPR14 mRNA expressions. These results suggested that diabetes-induced upregulation of UII and GPR14, most likely through autocrine and/or paracrine mechanisms, plays an important role in TGF-beta1-mediated renal fibrosis and dysfunction.

Authors+Show Affiliations

Department of Experimental Pharmacology and Toxicology, School of Pharmacy, Jilin University, Changchun, P.R.China.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

18796544

Citation

Tian, Lin, et al. "Diabetes-induced Upregulation of Urotensin II and Its Receptor Plays an Important Role in TGF-beta1-mediated Renal Fibrosis and Dysfunction." American Journal of Physiology. Endocrinology and Metabolism, vol. 295, no. 5, 2008, pp. E1234-42.
Tian L, Li C, Qi J, et al. Diabetes-induced upregulation of urotensin II and its receptor plays an important role in TGF-beta1-mediated renal fibrosis and dysfunction. Am J Physiol Endocrinol Metab. 2008;295(5):E1234-42.
Tian, L., Li, C., Qi, J., Fu, P., Yu, X., Li, X., & Cai, L. (2008). Diabetes-induced upregulation of urotensin II and its receptor plays an important role in TGF-beta1-mediated renal fibrosis and dysfunction. American Journal of Physiology. Endocrinology and Metabolism, 295(5), E1234-42. https://doi.org/10.1152/ajpendo.90672.2008
Tian L, et al. Diabetes-induced Upregulation of Urotensin II and Its Receptor Plays an Important Role in TGF-beta1-mediated Renal Fibrosis and Dysfunction. Am J Physiol Endocrinol Metab. 2008;295(5):E1234-42. PubMed PMID: 18796544.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Diabetes-induced upregulation of urotensin II and its receptor plays an important role in TGF-beta1-mediated renal fibrosis and dysfunction. AU - Tian,Lin, AU - Li,Cai, AU - Qi,Jiping, AU - Fu,Peng, AU - Yu,Xiaoyan, AU - Li,Xiaokun, AU - Cai,Lu, Y1 - 2008/09/16/ PY - 2008/9/18/pubmed PY - 2009/1/13/medline PY - 2008/9/18/entrez SP - E1234 EP - 42 JF - American journal of physiology. Endocrinology and metabolism JO - Am J Physiol Endocrinol Metab VL - 295 IS - 5 N2 - Urotensin II (UII) was identified as the ligand for a novel G protein-coupled receptor, GPR14. UII was found not only to have a potent vasoconstrictive action but also to have profibrotic effects in the heart. The present study was to define whether UII and GPR14 also play important roles in diabetes-induced renal fibrosis and dysfunction. Diabetic rats were induced using streptozotocin, and the rat proximal tubular epithelial cells (NRK-52E) were used for the in vitro mechanism study. Results showed that expression of UII and GPR14 was significantly upregulated at both mRNA and protein levels in the diabetic kidneys compared with controls. The upregulated expressions of UII and GPR14 in the kidney were accompanied by significant increases in the renal profibrotic factor transforming growth factor (TGF)-beta1 expression, the renal extracellular matrix (fibronectin and collagen IV) accumulation, and the renal dysfunction (increases in urinal N-acetyl-beta-d-glucosaminidase content, 24-h urinary retinol-binding protein excretion rate, and decrease in creatinine clearance rate). Exposure of NRK-52E cells to 10(-8) mol/l UII for 48 h caused a significant increase of TGF-beta1, but not ANG II, production that was GPR14- and calcium-dependent, since GPR14 small-interfering RNA and calcium channel blocker nimodipine or calcium chelator EDTA all could abolish the induction of TGF- beta1 by UII. Furthermore, exposure of NRK-52E cells to TGF-beta1 or ANG II also increased UII and GPR14 mRNA expressions. These results suggested that diabetes-induced upregulation of UII and GPR14, most likely through autocrine and/or paracrine mechanisms, plays an important role in TGF-beta1-mediated renal fibrosis and dysfunction. SN - 0193-1849 UR - https://www.unboundmedicine.com/medline/citation/18796544/Diabetes_induced_upregulation_of_urotensin_II_and_its_receptor_plays_an_important_role_in_TGF_beta1_mediated_renal_fibrosis_and_dysfunction_ L2 - https://journals.physiology.org/doi/10.1152/ajpendo.90672.2008?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -