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LIBRIS Formathandbok  (Information om MARC21)
FältnamnIndikatorerMetadata
00002958naa a2200373 4500
001oai:prod.swepub.kib.ki.se:135542595
003SwePub
008240811s2017 | |||||||||||000 ||eng|
024a http://kipublications.ki.se/Default.aspx?queryparsed=id:1355425952 URI
024a https://doi.org/10.1152/ajprenal.00564.20162 DOI
040 a (SwePub)ki
041 a engb eng
042 9 SwePub
072 7a ref2 swepub-contenttype
072 7a art2 swepub-publicationtype
100a Su, W4 aut
2451 0a Liver X receptor β increases aquaporin 2 protein level via a posttranscriptional mechanism in renal collecting ducts
264 1b American Physiological Society,c 2017
520 a Liver X receptors (LXRs) including LXRα and LXRβ are nuclear receptor transcription factors and play an important role in lipid and glucose metabolism. It has been previously reported that mice lacking LXRβ but not LXRα develop a severe urine concentrating defect, likely via a central mechanism. Here we provide evidence that LXRβ regulates water homeostasis through increasing aquaporin 2 (AQP2) protein levels in renal collecting ducts. LXRβ−/− mice exhibited a reduced response to desmopressin (dDAVP) stimulation, suggesting that the diabetes insipidus phenotype is of both central and nephrogenic origin. AQP2 protein abundance in the renal inner medulla was significantly reduced in LXRβ−/− mice but with little change in AQP2 mRNA levels. In vitro studies showed that AQP2 protein levels were elevated upon LXR agonist treatment in both primary cultured mouse inner medullary duct cells (mIMCD) and the mIMCD3 cell line with stably expressed AQP2. In addition, LXR agonists including TO901317 and GW3965 failed to induce AQP2 gene transcription but diminished its protein ubiquitination in primary cultured mIMCD cells, thereby inhibiting its degradation. Moreover, LXR activation-induced AQP2 protein expression was abolished by the protease inhibitor MG132 and the ubiquitination-deficient AQP2 (K270R). Taken together, the present study demonstrates that activation of LXRβ increases AQP2 protein levels in the renal collecting ducts via a posttranscriptional mechanism. As such, LXRβ represents a key regulator of body water homeostasis.
700a Huang, SZ4 aut
700a Gao, M4 aut
700a Kong, XM4 aut
700a Gustafsson, JAu Karolinska Institutet4 aut
700a Xu, SJ4 aut
700a Wang, B4 aut
700a Zheng, F4 aut
700a Chen, LH4 aut
700a Wang, NP4 aut
700a Guan, YF4 aut
700a Zhang, XY4 aut
710a Karolinska Institutet4 org
773t American journal of physiology. Renal physiologyd : American Physiological Societyg 312:4, s. F619-F628q 312:4<F619-F628x 1522-1466x 1931-857X
8564 8u http://kipublications.ki.se/Default.aspx?queryparsed=id:135542595
8564 8u https://doi.org/10.1152/ajprenal.00564.2016

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