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Sökning: WFRF:(Tryggvason K.) > Wolf-Hirschhorn syn...

LIBRIS Formathandbok  (Information om MARC21)
FältnamnIndikatorerMetadata
00003337naa a2200421 4500
001oai:prod.swepub.kib.ki.se:136108564
003SwePub
008240913s2017 | |||||||||||000 ||eng|
0247 a http://kipublications.ki.se/Default.aspx?queryparsed=id:1361085642 URI
0247 a https://doi.org/10.1152/ajprenal.00305.20162 DOI
040 a (SwePub)ki
041 a engb eng
042 9 SwePub
072 7a ref2 swepub-contenttype
072 7a art2 swepub-publicationtype
1001 a Ito, Y4 aut
2451 0a Wolf-Hirschhorn syndrome candidate 1-like 1 epigenetically regulates nephrin gene expression
264 1b American Physiological Society,c 2017
520 a Altered expression of nephrin underlies the pathophysiology of proteinuria in both congenital and acquired nephrotic syndrome. However, the epigenetic mechanisms of nephrin gene regulation remain elusive. Here, we show that Wolf-Hirschhorn syndrome candidate 1-like 1 long form (WHSC1L1-L) is a novel epigenetic modifier of nephrin gene regulation. WHSC1L1-L was associated with histone H3K4 and H3K36 in human embryonic kidney cells. WHSC1L1-L gene was expressed in the podocytes, and functional protein product was detected in these cells. WHSC1L1-L was found to bind nephrin but not other podocyte-specific gene promoters, leading to its inhibition/suppression, abrogating the stimulatory effect of WT1 and NF-κB. Gene knockdown of WHSC1L1-L in primary cultured podocytes accelerated the transcription of nephrin but not CD2AP. An in vivo zebrafish study involving the injection of Whsc1l1 mRNA into embryos demonstrated an apparent reduction of nephrin mRNA but not podocin and CD2AP mRNA. Immunohistochemistry showed that both WHSC1L1-L and nephrin emerged at the S-shaped body stage in glomeruli. Immunofluorescence and confocal microscopy displayed WHSC1L1 to colocalize with trimethylated H3K4 in the glomerular podocytes. Chromatin immunoprecipitation assay revealed the reduction of the association of trimethylated H3K4 at the nephrin promoter regions. Finally, nephrin mRNA was upregulated in the glomerulus at the early proteinuric stage of mouse nephrosis, which was associated with the reduction of WHSC1L1. In conclusion, our results demonstrate that WHSC1L1-L acts as a histone methyltransferase in podocytes and regulates nephrin gene expression, which may in turn contribute to the integrity of the slit diaphragm of the glomerular filtration barrier.
7001 a Katayama, K4 aut
7001 a Nishibori, Y4 aut
7001 a Akimoto, Y4 aut
7001 a Kudo, A4 aut
7001 a Kurayama, R4 aut
7001 a Hada, I4 aut
7001 a Takahashi, S4 aut
7001 a Kimura, T4 aut
7001 a Fukutomi, T4 aut
7001 a Katada, T4 aut
7001 a Suehiro, J4 aut
7001 a Beltcheva, O4 aut
7001 a Tryggvason, Ku Karolinska Institutet4 aut
7001 a Yan, K4 aut
7102 a Karolinska Institutet4 org
7730 t American journal of physiology. Renal physiologyd : American Physiological Societyg 312:6, s. F1184-F1199q 312:6<F1184-F1199x 1522-1466x 1931-857X
8564 u https://www.physiology.org/doi/pdf/10.1152/ajprenal.00305.2016
8564 8u http://kipublications.ki.se/Default.aspx?queryparsed=id:136108564
8564 8u https://doi.org/10.1152/ajprenal.00305.2016

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