共查询到20条相似文献,搜索用时 62 毫秒
1.
Human insulin gene is a target gene of hepatocyte nuclear factor-1alpha (HNF-1alpha) and HNF-1beta. 总被引:6,自引:0,他引:6
K Okita Q Yang K Yamagata K A Hangenfeldt J Miyagawa Y Kajimoto H Nakajima M Namba C B Wollheim T Hanafusa Y Matsuzawa 《Biochemical and biophysical research communications》1999,263(2):566-569
2.
3.
Structure/function studies of hepatocyte nuclear factor-1alpha, a diabetes-associated transcription factor 总被引:1,自引:0,他引:1
Yang Q Yamagata K Yamamoto K Miyagawa J Takeda J Iwasaki N Iwahashi H Yoshiuchi I Namba M Miyazaki J Hanafusa T Matsuzawa Y 《Biochemical and biophysical research communications》1999,266(1):196-202
4.
5.
6.
7.
8.
9.
10.
11.
12.
Gu N Adachi T Matsunaga T Takeda J Tsujimoto G Ishihara A Yasuda K Tsuda K 《Biochemical and biophysical research communications》2006,346(3):1016-1023
Dipeptidylpeptidase IV (DPP-IV) is a well-documented drug target for the treatment of type 2 diabetes. Hepatocyte nuclear factors (HNF)-1alpha and HNF-1beta, known as the causal genes of MODY3 and MODY5, respectively, have been reported to be involved in regulation of DPP-IV gene expression. But, it is not completely clear (i) that they play roles in regulation of DPP-IV gene expression, and (ii) whether DPP-IV gene activity is changed by mutant HNF-1alpha and mutant HNF-1beta in MODY3 and MODY5. To explore these questions, we investigated transactivation effects of wild HNF-1alpha and 13 mutant HNF-1alpha, as well as wild HNF-1beta and 2 mutant HNF-1beta, on DPP-IV promoter luciferase gene in Caco-2 cells by means of a transient experiment. Both wild HNF-1alpha and wild HNF-1beta significantly transactivated DPP-IV promoter, but mutant HNF-1alpha and mutant HNF-1beta exhibited low transactivation activity. Moreover, to study whether mutant HNF-1alpha and mutant HNF-1beta change endogenous DPP-IV enzyme activity, we produced four stable cell lines from Caco-2 cells, in which wild HNF-1alpha or wild HNF-1beta, or else respective dominant-negative mutant HNF-1alphaT539fsdelC or dominant-negative mutant HNF-1betaR177X, was stably expressed. We found that DPP-IV gene expression and enzyme activity were significantly increased in wild HNF-1alpha cells and wild HNF-1beta cells, whereas they decreased in HNF-1alphaT539fsdelC cells and HNF-1betaR177X cells, compared with DPP-IV gene expression and enzyme activity in Caco-2 cells. These results suggest that both wild HNF-1alpha and wild HNF-1beta have a stimulatory effect on DPP-IV gene expression, but that mutant HNF-1alpha and mutant HNF-1beta attenuate the stimulatory effect. 相似文献
13.
14.
15.
Mutations in the hepatocyte nuclear factor-1beta gene are associated with familial hypoplastic glomerulocystic kidney disease 总被引:3,自引:0,他引:3
下载免费PDF全文
![点击此处可从《American journal of human genetics》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Bingham C Bulman MP Ellard S Allen LI Lipkin GW Hoff WG Woolf AS Rizzoni G Novelli G Nicholls AJ Hattersley AT 《American journal of human genetics》2001,68(1):219-224
Familial glomerulocystic kidney disease (GCKD) is a dominantly inherited condition characterized by glomerular cysts and variable renal size and function; the molecular genetic etiology is unknown. Mutations in the gene encoding hepatocyte nuclear factor (HNF)-1beta have been associated with early-onset diabetes and nondiabetic renal disease-particularly renal cystic disease. We investigated a possible role for the HNF-1beta gene in four unrelated GCKD families and identified mutations in two families: a nonsense mutation in exon 1 (E101X) and a frameshift mutation in exon 2 (P159fsdelT). The family members with HNF-1beta gene mutations had hypoplastic GCKD and early-onset diabetes or impaired glucose tolerance. We conclude that there is genetic heterogeneity in familial GCKD and that the hypoplastic subtype is a part of the clinical spectrum of the renal cysts and diabetes syndrome that is associated with HNF-1beta mutations. 相似文献
16.
17.
18.
19.
20.
Dietary polyunsaturated fatty acids and regulation of gene transcription 总被引:18,自引:0,他引:18
Jump DB 《Current opinion in lipidology》2002,13(2):155-164