vHNF1 is expressed in epithelial cells of distinct embryonic origin during development and precedes HNF1 expression

Ott, Marie‐Odile; Rey-Campos, Javier; Cereghini, S.; Yaniv, Moshe

doi:10.1016/0925-4773(91)90071-d

Cited by 93 publications

(68 citation statements)

References 43 publications

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“…HNF1␣ and vHNF1, also called HNF1␤, share strong homologies in both the dimerization domain and the DNA binding domain and thus are able to form heterodimers and bind to the same DNA sequences (12). HNF1␣ and HNF1␤ are expressed in various organs, including the liver, kidney, stomach, and pancreas (13)(14)(15). The expression of HNF1␣ and HNF1␤ overlaps; however, in adult liver, HNF1␤ is weakly expressed but HNF1␣ is much more abundant (13)(14)(15).…”

Section: Discussionmentioning

confidence: 99%

Control of ACAT2 liver expression by HNF1

Pramfalk

Davis

Eriksson

et al. 2005

Journal of Lipid Research

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ACAT catalyzes the formation of cholesteryl esters from cholesterol and long-chain fatty acids. There are two known genes encoding the two ACAT enzymes, ACAT1 and ACAT2 (also known as Soat1 and Soat2). In adult humans, ACAT1 is present in most tissues, whereas ACAT2 is localized to enterocytes and hepatocytes. In this report, we elucidate the mechanisms that control the liver-specific expression of the human ACAT2 gene. We identified hepatic nuclear factor 1 (HNF1) as an important liver-specific transacting element for the human ACAT2 gene using the human hepatocellular carcinoma cell lines HuH7 and HepG2. Tar ACAT is an integral membrane protein of the rough endoplasmic reticulum that catalyzes the formation of cholesteryl esters from cholesterol and long-chain fatty acids (1). The solubility characteristics of cholesteryl esters make them the major choice for the storage of cholesterol, mostly as cytoplasmic lipid droplets inside the cells. Thus, ACAT is a key enzyme in the control of intracellular cholesterol storage and in determining the level of free cholesterol (2). There are two known genes that encode the two ACAT enzymes, ACAT1 and ACAT2, also known by international convention as steroyl O -acyltransferase (i.e., Soat1 and Soat2, respectively) (3). ACAT1 has been shown to be present in most tissues, whereas the location of ACAT2 has been relatively unclear. According to previous studies (4-6), ACAT2 is found mainly in the apical region of the intestinal villi and in human fetal liver, whereas ACAT1 is the major ACAT isoenzyme in adult human liver. However, we recently showed that ACAT2 is the major ACAT isoenzyme in adult human liver and that it is located in hepatocytes, whereas ACAT1 is located in Kupffer cells (7). This is consistent with similar findings in mice and nonhuman primates (8,9) and is also in agreement with the proposed role for ACAT2 in the assembly and secretion of cholesteryl esters in lipoproteins.Based on this new knowledge, ACAT2 may be a viable target for the treatment and prevention of diseases associated with cholesterol accumulation (e.g., atherosclerosis). Thus, it is of great importance to characterize the mechanisms involved in ACAT2 transcriptional regulation. In the present study, we identify an important liver-specific cis -acting element in the promoter region of ACAT2 that acts as a putative binding site for the hepatic nuclear factor 1 (HNF1). This element serves as a positive regulator of gene expression and is functionally active. Finally, by chromatin immunoprecipitation assay, we show that the transcription factors HNF1 ␣ and HNF1 ␤ bind to the identified promoter region of ACAT2 in vivo in human liver.

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Section: Discussionmentioning

confidence: 99%

Control of ACAT2 liver expression by HNF1

Pramfalk

Davis

Eriksson

et al. 2005

Journal of Lipid Research

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“…E-cadherin, which is normally expressed in the basolateral membrane of tubular cells, was down-regulated in atrophic tubules. Similarly, HNF-1␤, which is expressed in differentiated epithelia in the kidney and other organs, 28,29 was detected in the nuclei of all tubular epithelial cells in shamoperated kidneys. However, the number of cells expressing HNF-1␤ decreased in the dilated and atrophic tubules beginning 7 to 10 days after obstruction.…”

Section: Uuo Leads To the Loss Of A Mature Epithelial Phenotypementioning

confidence: 91%

Autophagy Is a Component of Epithelial Cell Fate in Obstructive Uropathy

Zepeda‐Orozco

Black

et al. 2010

The American Journal of Pathology

178

162

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Epithelial cell fate and nephron loss in obstructive uropathy are not fully understood. We produced transgenic mice in which epithelial cells in the nephrons and collecting ducts were labeled with enhanced yellow fluorescent protein, and tracked the fate of these cells following unilateral ureteral obstruction (UUO). UUO led to a decrease in the number of enhanced yellow fluorescent protein-expressing cells and down-regulation of epithelial markers, Ecadherin, and hepatocyte nuclear factor-1␤. Following UUO, enhanced yellow fluorescent protein-positive cells were confined within the tubular basement membrane, were not found in the renal interstitium, and did not express ␣-smooth muscle actin or S100A4, markers of myofibroblasts and fibroblasts. Moreover, when proximal tubules were labeled with dextran before UUO, dextran-retaining cells did not migrate into the interstitium or express ␣-smooth muscle actin. These results indicate that UUO leads to tubular epithelial loss but does not cause epithelial-tomesenchymal transition that has been shown by others to be responsible for nephron loss and interstitial fibrosis. For the first time, we found evidence of enhanced autophagy in obstructed tubules, including accumulation of autophagosomes, increased expression of Beclin 1, and increased conversion of microtubular-associated protein 1 light chain 3-I to -II. Increased autophagy may represent a mechanism of tubular survival or may contribute to excessive cell death and tubular atrophy after obstructive injury.

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“…An important criterion to evaluate the differentiation of the transplanted BMEL cells is expression of transcription factors in hepatocytes and bile duct cells. HNF1␣ and HNF4␣ are among the most characteristic markers of differentiated hepatocytes, whereas HNF1␤ is expressed more abundantly in bile duct cells than in hepatocytes, and HNF4␣ is absent from bile ducts (26)(27)(28). HNF1␣ (Fig.…”

Section: The Fine Regulation Of Transcription Factor Expression Is Rementioning

confidence: 99%