Sustained hyperosmolarity increses TGF-ß1 and Egr-1 expression in the rat renal medulla
Abstract Background Although 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 chr...
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| Format: | Article |
| Language: | English |
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BMC
2017-07-01
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| Series: | BMC Nephrology |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s12882-017-0626-2 |
| _version_ | 1818992421154848768 |
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| author | Miklós M. Mózes Petra Szoleczky László Rosivall Gábor Kökény |
| author_facet | Miklós M. Mózes Petra Szoleczky László Rosivall Gábor Kökény |
| author_sort | Miklós M. Mózes |
| collection | DOAJ |
| description | Abstract Background Although 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. Methods Male 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. Results Urine 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. Conclusion We 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. |
| first_indexed | 2024-12-20T20:25:53Z |
| format | Article |
| id | doaj.art-a9f68313ba6d48cc8b36fa5ab11179d5 |
| institution | Directory Open Access Journal |
| issn | 1471-2369 |
| language | English |
| last_indexed | 2024-12-20T20:25:53Z |
| publishDate | 2017-07-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Nephrology |
| spelling | doaj.art-a9f68313ba6d48cc8b36fa5ab11179d52022-12-21T19:27:29ZengBMCBMC Nephrology1471-23692017-07-0118111110.1186/s12882-017-0626-2Sustained hyperosmolarity increses TGF-ß1 and Egr-1 expression in the rat renal medullaMiklós M. Mózes0Petra Szoleczky1László Rosivall2Gábor Kökény3Institute of Pathophysiology, Semmelweis UniversityInstitute of Pathophysiology, Semmelweis UniversityInstitute of Pathophysiology, Semmelweis UniversityInstitute of Pathophysiology, Semmelweis UniversityAbstract Background Although 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. Methods Male 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. Results Urine 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. Conclusion We 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.http://link.springer.com/article/10.1186/s12882-017-0626-2Osmotic stressUreaSodium chlorideFibrosisTGF-ßEgr-1 |
| spellingShingle | Miklós M. Mózes Petra Szoleczky László Rosivall Gábor Kökény Sustained hyperosmolarity increses TGF-ß1 and Egr-1 expression in the rat renal medulla BMC Nephrology Osmotic stress Urea Sodium chloride Fibrosis TGF-ß Egr-1 |
| title | Sustained hyperosmolarity increses TGF-ß1 and Egr-1 expression in the rat renal medulla |
| title_full | Sustained hyperosmolarity increses TGF-ß1 and Egr-1 expression in the rat renal medulla |
| title_fullStr | Sustained hyperosmolarity increses TGF-ß1 and Egr-1 expression in the rat renal medulla |
| title_full_unstemmed | Sustained hyperosmolarity increses TGF-ß1 and Egr-1 expression in the rat renal medulla |
| title_short | Sustained hyperosmolarity increses TGF-ß1 and Egr-1 expression in the rat renal medulla |
| title_sort | sustained hyperosmolarity increses tgf ss1 and egr 1 expression in the rat renal medulla |
| topic | Osmotic stress Urea Sodium chloride Fibrosis TGF-ß Egr-1 |
| url | http://link.springer.com/article/10.1186/s12882-017-0626-2 |
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