Open AccessALPK1 regulates streptozotocin‐induced nephropathy through CCL2 and CCL5 expressions
Author(s) -
Lee ChiPin,
Nithiyanantham Srinivasan,
Hsu HuiTing,
Yeh KunTu,
Kuo TzerMin,
Ko YingChin
Publication year - 2019
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.14643
Subject(s) - ccl5 , streptozotocin , chemokine , kidney , endocrinology , ccl2 , medicine , masson's trichrome stain , diabetic nephropathy , diabetes mellitus , chemistry , inflammation , immunohistochemistry , immunology , immune system , t cell , il 2 receptor
ALPK1 is associated with chronic kidney disease, gout and type 2 diabetes mellitus. Raised renal ALPK1 level in patients with diabetes was reported. Accelerated fibrotic nephropathies were observed in hyperglycaemic mice with up‐regulated 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‐treated wild‐type mice (WT‐STZ) and streptozotocin‐treated ALPK1 transgenic mice (TG‐STZ). The ALPK1 levels were measured in mice kidney and in cultured cells. We found that the higher levels of renal CCL2/MCP‐1, CCL5/Rantes and G‐CSF expression in TG‐STZ compared with the WT‐STZ. Glucose increased ALPK1 expressions in monocytic THP1 and human kidney‐2 cells. The protein expression of ALPK1, NFkB and lectin was up‐regulated in glucose‐treated HK‐2 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‐regulation involving in diabetic nephropathies induction.