BMC Nephrology | |
Sustained hyperosmolarity increses TGF-ß1 and Egr-1 expression in the rat renal medulla | |
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
【 预 览 】
Files | Size | Format | View |
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RO202311105826231ZK.pdf | 6650KB | download |
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