In:
American Journal of Physiology-Renal Physiology, American Physiological Society, Vol. 303, No. 5 ( 2012-09-01), p. F689-F699
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 [ 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.
Type of Medium:
Online Resource
ISSN:
1931-857X
,
1522-1466
DOI:
10.1152/ajprenal.00086.2012
Language:
English
Publisher:
American Physiological Society
Publication Date:
2012
detail.hit.zdb_id:
1477287-5
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