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http://ir.nhri.org.tw/handle/3990099045/11800
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| Title: | O-GlcNAcylation disrupts STRA6-retinol signals in kidneys of diabetes |
| Authors: | Chen, CH;Lin, KD;Ke, LY;Liang, CJ;Kuo, WC;Lee, MY;Lee, YL;Hsiao, PJ;Hsu, CC;Shin, SJ |
| Contributors: | Institute of Population Health Sciences |
| Abstract: | BACKGROUND: O-GlcNAcylation is an important mechanism of diabetic complication. Retinoid homeostasis regulates cell-physiological functions through STRA6-retinol signaling. Therefore, we investigated whether O-GlcNAcylation disrupted STRA6-retinol signals in diabetes. METHODS: Immunoprecipitation and proximity ligation assay were used to investigate O-GlcNAcylation of STRA6-retinol signals in kidneys of db/db and ob/ob mice. Western blot and immunohistochemistry were done for STRA6/CRBP1/LRAT/RALDH1/RARs pathway, GFAT, OGT, TGFbeta1 and collagen 1 level. HPLC and ELISA for retinol, retinal, and retinoic acid concentrations were performed in vivo and vitro. RBP4 binding with STRA6 was measured in vitro. To verify whether O-GlcNAcylation disrupted STRA6-retinol signals, treatment of TMG and OSMI-1, transfection of OGA and OGT, and OGT siRNA were performed in HK-2 cells. RESULTS: STRA6 and RALDH1 were highly O-GlcNAc-modified in glomeruli and tubules of db/db and ob/ob mice. RBP4, p-Try, p-JAK2, and p-STAT5 on STRA6 immunoprecipitate were reduced. Cellular retinol signals (CRBP1, LRAT, ADH, retinol, retinal, RA, RARalpha, RARgamma and RXRalpha) remarkably decreased in kidneys of db/db, ob/ob mice and HG-cultured cells. TMG and OGT transfection induced O-GlcNAcylation of STRA6 and RALDH1, repressed RBP4-bound STRA6, and retinol signals in NG-cultured cells. OSMI-1, OGA transfection, and OGT silence reversed O-GlcNAc-modification of STRA6 and RALDH1, and rescued the decrease of retinol signals, and reversed the increase of TGFbeta1 and collagen 1 in HG-treated cells. CONCLUSIONS: O-GlcNAcylation significantly modified STRA6 and RALDH1, suppressed RBP4 binding activity, and disrupted retinol signals in the kidney of diabetes. GENERAL SIGNIFICANCE: This study first indicates that STRA6-retinol signals were directly disrupted by O-GlcNAcylation in diabetic kidney. |
| Date: | 2019-06 |
| Relation: | Biochimica et Biophysica Acta. General Subjects. 2019 Jun;1863(6):1059-1069. |
| Link to: | http://dx.doi.org/10.1016/j.bbagen.2019.03.014 |
| JIF/Ranking 2023: | http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=0304-4165&DestApp=IC2JCR |
| Cited Times(WOS): | https://www.webofscience.com/wos/woscc/full-record/WOS:000467888000007 |
| Cited Times(Scopus): | https://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=85063859183 |
| Appears in Collections: | [許志成] 期刊論文
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| PUB30905621.pdf | 15191Kb | Adobe PDF | 348 | View/Open |
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