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. (August 2022)

• Record Type: Journal Article
• Authors: Du, Chunyang; Zhu, Yan; Yang, Yan; Mu, Lin; Yan, Xue; Wu, Ming; Zhou, Chenming; Wu, Haijiang; Zhang, Wei; Wu, Yanhui; Zhang, Guoyu; Hu, Yue; Ren, Yunzhuo; Shi, Yonghong
• Is Part Of: International journal of biochemistry & cell biology. Volume 149(2022)
• Publication Date: 2022-08
• Subjects: DN diabetic nephropathy -- AKI acute kidney injury -- CKD chronic kidney disease -- EMT epithelial to mesenchymal transition -- NLRP3 nucleotide-binding oligomerization domain-like pyrin domain containing protein 3 -- RIPK receptor interacting serine–threonine protein kinase -- MLKL mixed lineage kinase domain-like -- CTRP3 C1q/tumor necrosis factor-related protein-3 -- STZ streptozotocin -- PA palmitic acid -- FBS fetal bovine serum -- NG normal glucose -- HG high glucose -- AraA adenine 9-β-D-arabinofuranoside -- MCP-1 monocyte chemoattractant protein-1 -- NSA necrosulfonamide -- IL-1β interleukin-1β -- IL-18 interleukin-18 -- SREBP-1 sterol regulatory element-binding protein-1 -- PPARα peroxisome proliferator-activated receptor α -- ABCA1 ATP-binding cassette transporter -- AMPK adenosine 5′-monophosphate activated protein kinase; C1q/tumor necrosis factor-related protein-3 -- Lipid accumulation -- Necroinflammation -- Diabetic nephropathy -- Adenosine monophosphate-activated protein kinase; Biochemistry -- Periodicals; Cytology -- Periodicals; Biochemistry -- Periodicals; Cell Biology -- Periodicals; Biochimie -- Périodiques; Cytologie -- Périodiques; Biochimie; Cytologie; Biochemistry; Cytology; Ressource Internet (Descripteur de forme); Périodique électronique (Descripteur de forme); Periodicals; 572.05
• DOI: 10.1016/j.biocel.2022.106247
• Languages: English
• ISSNs: 1357-2725

Abstract

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.