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  3. C1q/tumour necrosis factor-related protein-3 alleviates high-glucose-induced lipid accumulation and necroinflammation in renal tubular cells by activating the adenosine monophosphate-activated protein kinase pathway

C1q/tumour necrosis factor-related protein-3 alleviates high-glucose-induced lipid accumulation and necroinflammation in renal tubular cells by activating the adenosine monophosphate-activated protein kinase pathway

  • Int J Biochem Cell Biol. 2022 Aug;149:106247. doi: 10.1016/j.biocel.2022.106247.
Chunyang Du 1,  Yan Zhu 2,  Yan Yang 3,  Lin Mu 3,  Xue Yan 4,  Ming Wu 3,  Chenming Zhou 5,  Haijiang Wu 1,  Wei Zhang 3,  Yanhui Wu 6,  Guoyu Zhang 6,  Yue Hu 6,  Yunzhuo Ren 7,  Yonghong Shi 8
Affiliations

Affiliations

  • 1 Department of Pathology, Hebei Medical University, Key Laboratory of Kidney Diseases of Hebei Province, Shijiazhuang, China; Center of Metabolic Diseases and Cancer research, Institute of Medical and Health Science, Hebei Medical University, Shijiazhuang 050017, China.
  • 2 Laboratorical center for Electron Microscopy, Hebei Medical University, Shijiazhuang, China.
  • 3 Department of Pathology, Hebei Medical University, Key Laboratory of Kidney Diseases of Hebei Province, Shijiazhuang, China.
  • 4 Department of Pediatrics, the 2nd Affiliated Hospital of Hebei Medical University, Shijiazhuang, China.
  • 5 Center of Metabolic Diseases and Cancer research, Institute of Medical and Health Science, Hebei Medical University, Shijiazhuang 050017, China.
  • 6 Clinical Medicine, College of Basic Medicine, Hebei Medical University, Shijiazhuang, China.
  • 7 Department of Pathology, Hebei Medical University, Key Laboratory of Kidney Diseases of Hebei Province, Shijiazhuang, China; Center of Metabolic Diseases and Cancer research, Institute of Medical and Health Science, Hebei Medical University, Shijiazhuang 050017, China. Electronic address: renyunzhuo1978@163.com.
  • 8 Department of Pathology, Hebei Medical University, Key Laboratory of Kidney Diseases of Hebei Province, Shijiazhuang, China; Center of Metabolic Diseases and Cancer research, Institute of Medical and Health Science, Hebei Medical University, Shijiazhuang 050017, China. Electronic address: yonghongshi@163.com.
PMID: 35753650 DOI: 10.1016/j.biocel.2022.106247
Abstract

Lipid accumulation and progressive necroinflammation play pivotal roles in the development of diabetic nephropathy. C1q tumour necrosis factor-related protein-3 (CTRP3) is an adipokine with pleiotropic functions in cell proliferation, glucose and lipid metabolism, and inflammation. However, the mechanism and involvement of CTRP3 in lipid metabolism and the necroinflammation of renal tubular cells remain unclear. Here, we report that CTRP3 expression decreased in a time- and concentration-dependent manner in high glucose-stimulated HK-2 cells. We noted that the overexpression of CTRP3 or recombinant CTRP3 (rCTRP3) treatment prevented high glucose-induced lipid accumulation by inhibiting the expression of sterol regulatory element-binding protein-1 and increasing the expression of peroxisome proliferator-activated receptor-α and ATP-binding cassette A1. Moreover, the nucleotide-binding oligomerisation domain-like receptor protein 3-mediated inflammatory response and Mixed Lineage Kinase domain-like protein-dependent necroinflammation were inhibited by CTRP3 overexpression or rCTRP3 treatment in HK-2 cells cultured in high glucose. Furthermore, lipotoxicity-induced by palmitic acid was found to be involved in necroinflammation in HK-2 cells, and CTRP3 displayed the same protective effect. CTRP3 also activated the adenosine monophosphate-activated protein kinase (AMPK) pathway, whereas adenine 9-β-D-arabinofuranoside, an AMPK Inhibitor, replicated the protective effects of CTRP3. Besides, using kidney biopsies from patients with diabetes, we found that decreased CTRP3 expression was accompanied by increased lipid deposition, as well as the structural and functional injury of renal tubular cells. Our findings demonstrate that CTRP3 affects lipid metabolism and necroinflammation in renal tubular cells via the AMPK signalling pathway. Thus, CTRP3 may be a potential therapeutic target in diabetic renal injury.

Keywords

Adenosine monophosphate-activated protein kinase; C1q/tumor necrosis factor-related protein-3; Diabetic nephropathy; Lipid accumulation; Necroinflammation.

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