Expression and Potential roles of Collectin-11 in Experimental Models of Chronic Kidney Disease

Chronic kidney disease (CKD) is a common disease, which affects nearly 10% of the global population. Although some new therapies have been developed in recent years, CKD is still difficult to treat. Renal fibrosis is a key characteristic in the progression of CKD to end-stage renal disease. This fibrotic process in the kidney may be initiated by complement activation, inflammation, intrinsic cell damage and excessive extracellular matrix deposition. However, the mechanisms of complement pathways in non-disease specific inflammation, tissue injury and fibrosis remain unclear. Collectin-11 (CL-11) is a component of the lectin pathway of complement activation combines with sugars to form a complex with mannose-binding lectinassociated serine protease-2 (MASP2) to trigger complement activation and may thus participate in the process of chronic kidney disease. The aim of this study is to investigate CL-11 expression in albumin overloaded kidney epithelial TCMK-1 cells, mouse adriamycin nephropathy and unilateral ureteral obstruction (UUO) models, to identify its role in the mechanisms involved in inflammation and renal fibrosis. The localization and dynamic changes of CL-11 protein and mRNA expression were studied by immunostaining, western blotting and reverse transcription polymerase chain reaction (RT-PCR). The CL-11 expression in TCMK-1 cells fluctuated in time course experiments, it was unrelated to incubation time and albumin concentration. The expression of C3 at the RNA level was time dependent, the expression of TGF-ꞵ1 also fluctuated. In reliminary adriamycin nephropathy studies, the increase in concentration of adriamycin may lead to an increase trend of CL-11 expression, but further experiments are needed for verification. The renal function of UUO mice decreased in 14 days. At an early stage knocking down MASP2 increased CL-11 expression in the sham group but decreased it in the UUO group. The expression of C3 was increased over time. Most importantly, when the complement MASP2 was absent, inflammation, apoptotic and fibrosis of the kidneys were significantly reduced. In conclusion, albumin can be toxic to TCMK-1 cells as shown by changes in the expression of CL-11. The expression of CL-11, C3, and TGF-ꞵ1 was varied in TCMK- 1 cells stimulated with different concentrations of albumin. The dosage of adriamycin used in this study had toxic effects on C57BL/6 mice that need to be optimized. MASP2-/- reduced inflammatory and apoptosis, as well as fibrosis, in which MASP2 may act together with CL-11 via lectin pathway.