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Role of nuclear factor of activated T-cells 5 in regulating hypertonic-mediated secretin receptor expression in kidney collecting duct cells
Chua O.W.H.1; Wong K.K.L.1; Ko B.C.2; Chung S.K.1; Chow B.K.C.1; Lee L.T.O.3
2016-07-01
Source PublicationBiochimica et Biophysica Acta - Gene Regulatory Mechanisms
ISSN18764320 18749399
Volume1859Issue:7Pages:922-932
AbstractA growing body of evidence suggests that secretin (SCT) is an important element in the osmoregulatory pathway. It is interesting to note that both SCT and its receptor (SCTR) gene are activated upon hyperosmolality in the kidney. However, the precise molecular mechanisms underlying the induction of the SCTR gene expression in response to changes in osmolality have yet to be clarified. Detailed DNA sequence analysis of the promoter regions of the SCTR gene reveals the presence of multiple osmotic response elements (ORE). The ORE is the binding site of a key osmosensitive transactivator, namely, the nuclear factor of activated T-cells 5 (NFAT5). SCTR and NFAT5 are co-expressed in the kidney cortex and medulla collecting duct cells. We therefore hypothesize that NFAT5 is responsible for modulating SCTR expression in hypertonic environments. In this study, we found hypertonicity stimulates the promoter activities and endogenous gene expression of SCTR in mouse kidney cortex collecting duct cells (M1) and inner medulla collecting duct cells (mIMCD3). The overexpression and silencing of NFAT5 further confirmed it to be responsible for the up-regulation of the SCTR gene under hypertonic conditions. A significant increase in the interaction between NFAT5 and the SCTR promoter was also observed following chromatin immunoprecipitation assay. In vivo, osmotic stress up-regulates the SCTR gene in the kidney cortex and medulla of wild-type mice, but does not do so in NFAT5 animals. Hence, this study provides comprehensive information on how NFAT5 regulates SCTR expression in different osmotic environments.
KeywordHypertonicity Nuclear factor of activated T-cells 5 Osmoregulation Secretin receptor Transcriptional regulation
DOI10.1016/j.bbagrm.2015.12.009
URLView the original
Language英語
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Cited Times [WOS]:1   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionFaculty of Health Sciences
Affiliation1.The University of Hong Kong
2.Hong Kong Polytechnic University
3.Universidade de Macau
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Chua O.W.H.,Wong K.K.L.,Ko B.C.,et al. Role of nuclear factor of activated T-cells 5 in regulating hypertonic-mediated secretin receptor expression in kidney collecting duct cells[J]. Biochimica et Biophysica Acta - Gene Regulatory Mechanisms,2016,1859(7):922-932.
APA Chua O.W.H.,Wong K.K.L.,Ko B.C.,Chung S.K.,Chow B.K.C.,&Lee L.T.O..(2016).Role of nuclear factor of activated T-cells 5 in regulating hypertonic-mediated secretin receptor expression in kidney collecting duct cells.Biochimica et Biophysica Acta - Gene Regulatory Mechanisms,1859(7),922-932.
MLA Chua O.W.H.,et al."Role of nuclear factor of activated T-cells 5 in regulating hypertonic-mediated secretin receptor expression in kidney collecting duct cells".Biochimica et Biophysica Acta - Gene Regulatory Mechanisms 1859.7(2016):922-932.
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