| http://purl.uniprot.org/citations/28604386 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/28604386 | http://www.w3.org/2000/01/rdf-schema#comment | "Autosomal dominant polycystic kidney disease (ADPKD) is driven by mutations in PKD1 and PKD2 genes. Recent work suggests that epigenetic modulation of gene expression and protein function may play a role in ADPKD pathogenesis. In this study, we identified SMYD2, a SET and MYND domain protein with lysine methyltransferase activity, as a regulator of renal cyst growth. SMYD2 was upregulated in renal epithelial cells and tissues from Pkd1-knockout mice as well as in ADPKD patients. SMYD2 deficiency delayed renal cyst growth in postnatal kidneys from Pkd1 mutant mice. Pkd1 and Smyd2 double-knockout mice lived longer than Pkd1-knockout mice. Targeting SMYD2 with its specific inhibitor, AZ505, delayed cyst growth in both early- and later-stage Pkd1 conditional knockout mouse models. SMYD2 carried out its function via methylation and activation of STAT3 and the p65 subunit of NF-κB, leading to increased cystic renal epithelial cell proliferation and survival. We further identified two positive feedback loops that integrate epigenetic regulation and renal inflammation in cyst development: SMYD2/IL-6/STAT3/SMYD2 and SMYD2/TNF-α/NF-κB/SMYD2. These pathways provide mechanisms by which SMYD2 might be induced by cyst fluid IL-6 and TNF-α in ADPKD kidneys. The SMYD2 transcriptional target gene Ptpn13 also linked SMYD2 to other PKD-associated signaling pathways, including ERK, mTOR, and Akt signaling, via PTPN13-mediated phosphorylation."xsd:string |
| http://purl.uniprot.org/citations/28604386 | http://purl.org/dc/terms/identifier | "doi:10.1172/jci90921"xsd:string |
| http://purl.uniprot.org/citations/28604386 | http://purl.uniprot.org/core/author | "Li X."xsd:string |
| http://purl.uniprot.org/citations/28604386 | http://purl.uniprot.org/core/author | "Zhou J.X."xsd:string |
| http://purl.uniprot.org/citations/28604386 | http://purl.uniprot.org/core/author | "Sage J."xsd:string |
| http://purl.uniprot.org/citations/28604386 | http://purl.uniprot.org/core/author | "Calvet J.P."xsd:string |
| http://purl.uniprot.org/citations/28604386 | http://purl.uniprot.org/core/author | "Li L.X."xsd:string |
| http://purl.uniprot.org/citations/28604386 | http://purl.uniprot.org/core/author | "Grantham J.J."xsd:string |
| http://purl.uniprot.org/citations/28604386 | http://purl.uniprot.org/core/author | "Fan L.X."xsd:string |
| http://purl.uniprot.org/citations/28604386 | http://purl.uniprot.org/core/date | "2017"xsd:gYear |
| http://purl.uniprot.org/citations/28604386 | http://purl.uniprot.org/core/name | "J Clin Invest"xsd:string |
| http://purl.uniprot.org/citations/28604386 | http://purl.uniprot.org/core/pages | "2751-2764"xsd:string |
| http://purl.uniprot.org/citations/28604386 | http://purl.uniprot.org/core/title | "Lysine methyltransferase SMYD2 promotes cyst growth in autosomal dominant polycystic kidney disease."xsd:string |
| http://purl.uniprot.org/citations/28604386 | http://purl.uniprot.org/core/volume | "127"xsd:string |
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