ALPK1 regulates streptozotocin-induced nephropathy through CCL2 and CCL5 expressions

J Cell Mol Med. 2019 Nov;23(11):7699-7708. doi: 10.1111/jcmm.14643. Epub 2019 Sep 26.


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.

Keywords: ALPK1; CCL2; CCL5; chemokine; diabetic nephropathy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line
  • Chemokine CCL2 / genetics*
  • Chemokine CCL2 / metabolism
  • Chemokine CCL5 / genetics*
  • Chemokine CCL5 / metabolism
  • Chemokines / metabolism
  • Glucose / toxicity
  • Humans
  • Kidney / pathology
  • Kidney Diseases / chemically induced*
  • Kidney Diseases / genetics*
  • Kidney Diseases / pathology
  • Male
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • NF-kappa B / metabolism
  • Protein Kinases / metabolism*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Streptozocin
  • Up-Regulation / drug effects
  • Up-Regulation / genetics


  • Chemokine CCL2
  • Chemokine CCL5
  • Chemokines
  • NF-kappa B
  • RNA, Messenger
  • Streptozocin
  • Protein Kinases
  • ALPK1 protein, human
  • Glucose