Upregulation of HNF-1β during experimental acute kidney injury plays a crucial role in renal tubule regeneration.
In: American journal of physiology. Renal physiology, Jg. 303 (2012-09-01), Heft 5, S. F689-99
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Zugriff:
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 [(3)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.
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Upregulation of HNF-1β during experimental acute kidney injury plays a crucial role in renal tubule regeneration.
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Autor/in / Beteiligte Person: | Ogata, K ; Shimamura, Y ; Hamada, K ; Hisa, M ; Bun, M ; Okada, N ; Inoue, K ; Taniguchi, Y ; Ishihara, M ; Kagawa, T ; Horino, T ; Fujimoto, S ; Terada, Y |
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Zeitschrift: | American journal of physiology. Renal physiology, Jg. 303 (2012-09-01), Heft 5, S. F689-99 |
Veröffentlichung: | Bethesda, Md. : American Physiological Society, c1997-, 2012 |
Medientyp: | academicJournal |
ISSN: | 1522-1466 (electronic) |
DOI: | 10.1152/ajprenal.00086.2012 |
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