Sustained hyperosmolarity increses TGF-ß1 and Egr-1 expression in the rat renal medulla

BMC Nephrology

Research Article

Petra Szoleczky¹  Gábor Kökény¹  Miklós M. Mózes¹  László Rosivall² 

[1] Institute of Pathophysiology, Semmelweis University, Nagyvárad tér 4, H-1089, Budapest, Hungary;Institute of Pathophysiology, Semmelweis University, Nagyvárad tér 4, H-1089, Budapest, Hungary;Hungarian Academy of Sciences and Semmelweis University Research Group for Pediatrics and Nephrology, Budapest, Hungary;

关键词: Osmotic stress;    Urea;    Sodium chloride;    Fibrosis;    TGF-ß;    Egr-1;   

DOI  :  10.1186/s12882-017-0626-2

 received in 2017-01-09, accepted in 2017-06-20,  发布年份 2017

来源: Springer

【 摘 要 】

BackgroundAlthough TGF-ß and the transcription factor Egr-1 play an important role in both kidney fibrosis and in response to acute changes of renal medullary osmolarity, their role under sustained hypo- or hyperosmolar conditions has not been elucidated. We investigated the effects of chronic hypertonicity and hypotonicity on the renal medullary TGF-ß and Egr-1 expression.MethodsMale adult Sprague Dawley rats (n = 6/group) were treated with 15 mg/day furosemide, or the rats were water restricted to 15 ml/200 g body weight per day. Control rats had free access to water and rodent chow. Kidneys were harvested after 5 days of treament.In cultured inner medullary collecting duct (IMCD) cells, osmolarity was increased from 330 mOsm to 900 mOsm over 6 days. Analyses were performed at 330, 600 and 900 mOsm.ResultsUrine osmolarity has not changed due to furosemide treatment but increased 2-fold after water restriction (p < 0.05). Gene expression of TGF-ß and Egr-1 increased by 1.9-fold and 7-fold in the hypertonic medulla, respectively (p < 0.05), accompanied by 6-fold and 2-fold increased c-Fos and TIMP-1 expression, respectively (p < 0.05) and positive immunostaining for TGF-ß and Egr-1 (p < 0.05).Similarly, hyperosmolarity led to overexpression of TGF-ß and Egr-1 mRNA in IMCD cells (2.5-fold and 3.5-fold increase from 330 to 900 mOsm, respectively (p < 0.05)) accompanied by significant c-Fos and c-Jun overexpressions (p < 0.01), and increased Col3a1 and Col4a1 mRNA expression.ConclusionWe conclude that both TGF-ß and Egr-1 are upregulated by sustained hyperosmolarity in the rat renal medulla, and it favors the expression of extracellular matrix components.

【 授权许可】

CC BY   
© The Author(s). 2017