Collectin-11 Promotes the Development of Renal Tubulointerstitial Fibrosis

• Published in: Journal of the American Society of Nephrology 2018-01, Vol.29 (1), p.168-181
• Main Authors: Wu, Weiju, Liu, Chengfei, Farrar, Conrad A, Ma, Liang, Dong, Xia, Sacks, Steven H, Li, Ke, Zhou, Wuding
• Format: Article
• Language: English
• Subjects: Allografts - pathology; Animals; Basic Research; Cell Proliferation - drug effects; Chemotaxis, Leukocyte - drug effects; Chemotaxis, Leukocyte - genetics; Collagen - metabolism; Collectins - genetics; Collectins - metabolism; Collectins - pharmacology; Extracellular Matrix - metabolism; Fibroblasts - physiology; Fibrosis; Kidney Transplantation; Kidney Tubules - metabolism; Kidney Tubules - pathology; Male; Mice; Mice, Knockout; Nephritis - etiology; Nephritis - genetics; Nephritis - pathology; Nephritis - physiopathology; Reperfusion Injury - complications; Reperfusion Injury - pathology
• ISSN: 1046-6673; 1533-3450
• DOI: 10.1681/asn.2017050544

Collectin-11 is a recently described soluble C-type lectin, a pattern recognition molecule of the innate immune system that has distinct roles in host defense, embryonic development, and acute inflammation. However, little is known regarding the role of collectin-11 in tissue fibrosis. Here, we investigated collectin-11 in the context of renal ischemia-reperfusion injury. Compared with wild-type littermate controls, deficient ( ) mice had significantly reduced renal functional impairment, tubular injury, renal leukocyte infiltration, renal tissue inflammation/fibrogenesis, and collagen deposition in the kidneys after renal ischemia-reperfusion injury. , recombinant collectin-11 potently promoted leukocyte migration and renal fibroblast proliferation in a carbohydrate-dependent manner. Additionally, compared with wild-type kidney grafts, kidney grafts displayed significantly reduced tubular injury and collagen deposition after syngeneic kidney transplant. Our findings demonstrate a pathogenic role for collectin-11 in the development of tubulointerstitial fibrosis and suggest that local collectin-11 promotes this fibrosis through effects on leukocyte chemotaxis and renal fibroblast proliferation. This insight into the pathogenesis of tubulointerstitial fibrosis may have implications for CKD mediated by other causes as well.