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Raised renal ALPK1 level in patients with diabetes was reported. Accelerated fibrotic nephropathies were observed in hyperglycaemic mice with up\u2010regulated ALPK1. The aim of this study was to identify the mediators contributing to ALPK1 effect involving in nephropathies induction. The haematoxylin and eosin staining, Masson's trichrome and immunohistochemical analysis of ALPK1, NFkB, CCL2 and CCL5 were performed in the mice kidney. Cytokine antibody array analysis was performed in streptozotocin\u2010treated wild\u2010type mice (WT\u2010STZ) and streptozotocin\u2010treated ALPK1 transgenic mice (TG\u2010STZ). The ALPK1 levels were measured in mice kidney and in cultured cells. We found that the higher levels of renal CCL2\/MCP\u20101, CCL5\/Rantes and G\u2010CSF expression in TG\u2010STZ compared with the WT\u2010STZ. Glucose increased ALPK1 expressions in monocytic THP1 and human kidney\u20102 cells. The protein expression of ALPK1, NFkB and lectin was up\u2010regulated in glucose\u2010treated HK\u20102 cells. Knockdown of ALPK1 reduced CCL2 and CCL5 mRNA levels, whereas overexpressed ALPK1 increased CCL2 and CCL5 in cultured kidney cells. Taken together, these results show that high glucose increases ALPK1 and chemokine levels in the kidney. Elevated ALPK1 expression enhances renal CCL2 and CCL5 expressions in vivo and in vitro. ALPK1 is a mediator for CCL2 and CCL5 chemokine up\u2010regulation involving in diabetic nephropathies induction.<\/jats:p>","DOI":"10.1111\/jcmm.14643","type":"journal-article","created":{"date-parts":[[2019,9,26]],"date-time":"2019-09-26T22:26:50Z","timestamp":1569536810000},"page":"7699-7708","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["ALPK1 regulates streptozotocin\u2010induced nephropathy through CCL2 and CCL5 expressions"],"prefix":"10.1111","volume":"23","author":[{"given":"Chi\u2010Pin","family":"Lee","sequence":"first","affiliation":[{"name":"Environment\u2010Omics\u2010Disease Research Center China Medical University Hospital China Medical University Taichung 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Medical University Hospital China Medical University Taichung Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying\u2010Chin","family":"Ko","sequence":"additional","affiliation":[{"name":"Environment\u2010Omics\u2010Disease Research Center China Medical University Hospital China Medical University Taichung Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,9,26]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.3892\/br.2015.439"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmedgenet-2013-101518"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1093\/ije\/dyt028"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2202-12-1"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jsbmb.2015.08.007"},{"issue":"4","key":"e_1_2_9_7_1","first-page":"654","article-title":"URAT1 inhibition by ALPK1 is 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