NLRC5 deficiency ameliorates diabetic nephropathy through alleviating inflammation.

Abstract

NOD-like receptor family caspase recruitment domain family domain containing 5 (NLRC5) has important roles in inflammation and innate immunity. NLRC5 was highly expressed in kidney from streptozotocin-induced diabetic mice, db/ db mice and patients with diabetes. Based on that evidence, the present study was designed to explore the roles of NLRC5 in the progression of diabetic nephropathy (DN). We examined kidney injury, including inflammation and fibrosis in Nlrc5 gene knockout ( Nlrc5-/-) and wild-type (WT) diabetic mice. We found that Nlrc5-/- mice developed less-severe diabetic kidney injury compared with WT mice, exhibiting lower albuminuria, less fibronectin and collagen IV expression, and reduced macrophage infiltration but greater levels of podocin and nephrin in the diabetic kidney. The underlying mechanisms were further investigated in vitro with peritoneal macrophages and mesangial cells treated with high glucose. Reduced proinflammatory effect was observed in peritoneal macrophages from Nlrc5-/- mice, associated with NF-κB pathway suppression. Knocking down of NLRC5 in mesangial cells in high-glucose conditions was also associated with reduced NF-κB and TGF-β/Smad signaling. Taken together, NLRC5 promotes inflammation and fibrosis during DN progression partly through the effects on NF-κB and TGF-β/Smad pathways. NLRC5 may, therefore, be a promising therapeutic target for DN treatment.-Luan, P., Zhuang, J., Zou, J., Li, H., Shuai, P., Xu, X., Zhao, Y., Kou, W., Ji, S., Peng, A., Xu, Y., Su, Q., Jian, W., Peng, W. NLRC5 deficiency ameliorates diabetic nephropathy through alleviating inflammation.

• Authors: Peipei Luan, Jianhui Zhuang, Jun Zou, Hailing Li, Ping Shuai, Xiaopeng Xu, Yifan Zhao, Wenxin Kou, Shuya Ji, Ai Peng, Yawei Xu, Qing Su, Weixia Jian, Wenhui Peng
• Journal: FASEB journal : official publication of the Federation of American Societies for Experimental Biology (FASEB J) Vol. 32 Issue 2 Pg. 1070-1084 (02 2018) ISSN: 1530-6860 [Electronic] United States
• PMID: 29070585 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Intracellular Signaling Peptides and Proteins
• NF-kappa B
• NLRC5 protein, human
• Smad Proteins
• Transforming Growth Factor beta

Topics

• Animals
• Diabetes Mellitus, Experimental (genetics, metabolism, pathology)
• Diabetic Nephropathies (genetics, metabolism, pathology)
• Female
• Humans
• Inflammation (genetics, metabolism, pathology)
• Intracellular Signaling Peptides and Proteins (deficiency)
• Male
• Mesangial Cells (metabolism, pathology)
• Mice
• Mice, Knockout
• NF-kappa B (genetics, metabolism)
• Signal Transduction
• Smad Proteins (genetics, metabolism)
• Transforming Growth Factor beta (genetics, metabolism)