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Upregulation of HNF-1β during experimental acute kidney injury plays a crucial role in renal tubule regeneration.
- Source :
- American Journal of Physiology: Renal Physiology; Sep2012, Vol. 303 Issue 5, pF689-F699, 11p
- Publication Year :
- 2012
-
Abstract
- Hepatocyte nuclear factor-1β (HNF-1β) is a transcription factor expressed in the kidney, liver, pancreas, and other organs. Mutations of HNF-1β cause maturity- onset diabetes of the young type 5 (MODY5). The aims of this study were to investigate the functional roles of the HNF-1β/suppressor of cytokine signaling-3 (SOCS-3) pathway in tubule damage after acute kidney injury (AKI) both in vivo and in vitro and to examine the effect of HNF-1β on renal tubule formation. To clarify the significance of the HNF-1β/SOCS-3 pathway in AKI, we used a rat ischemia/reperfusion (I/R) AKI model and cultured renal tubular cells (NRK-52E cells). Western blot analysis showed that HNF-1β and polycystic kidney disease 2 (PKD2) expressions were increased at 3-12 h and 12-24 h after I/R, respectively. The expression level of SOCS-3 was decreased at 3-48 h. Immunohistological examination revealed that expression of HNF-1β was increased in proximal tubules. Overexpression of HNF-1β resulted in decreased SOCS-3 expression, activation of signal transducer and activator of transcription 3 (STAT3) and Erk, and increased [<superscript>3</superscript>H]thymidine uptake in the presence of hepatocyte growth factor. Furthermore, tubule formation in three-dimensional gels was inhibited by dominant-negative HNF- 1β. Our study shows that HNF-1β is upregulated after AKI in proximal tubular cells and that HNF-1β controls cellular proliferation and tubule formation by regulating SOCS-3 expression and STAT3/ Erk activation. Therefore, the current study unravels the physiological and pathological significance of the HNF-1β pathway in AKI. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 1931857X
- Volume :
- 303
- Issue :
- 5
- Database :
- Complementary Index
- Journal :
- American Journal of Physiology: Renal Physiology
- Publication Type :
- Academic Journal
- Accession number :
- 95856643
- Full Text :
- https://doi.org/10.1152/ajprenal.00086.2012