Objective Macrophage-mediated inflammation plays a significant role in the development and progression of diabetic nephropathy (DN). However, the underlying mechanisms remain unclear. Studies suggest that T cell immunoglobulin domain and mucin domain-3 (Tim-3) has complicated roles in regulating macrophage activation, but its roles in the progression of DN are still completely unknown. Methods We downregulated Tim-3 expression in kidney (intrarenal injection of Tim-3 shRNA expressing lentivirus or global Tim-3 knockout mice) and induced DN by streptozotocin (STZ). We analyzed the degree of renal injury, especially the podocyte injury induced by activated macrophages in vitro and in vivo . Then, we transferred different bone marrow derived macrophages (BMs) into STZ-induced Tim-3 knockdown mice to examine the effects of Tim-3 on macrophages in DN. Results First, we found that Tim-3 expression on renal macrophages was increased in patients with DN and in two diabetic mouse models, i.e. STZ-induced diabetic mice and db/db mice, and positively correlated with renal dysfunction of DN patients. Tim-3 deficiency ameliorated renal damage in STZ-induced diabetes with concurrent increase in protein levels of Nephrin and WT-1. Similar effects were observed in mice with Tim-3 knockdown diabetic mice. Second, adoptive transfer of Tim-3-expressing macrophages, but not Tim-3 knockout macrophages, accelerated diabetic renal injury in DN mice, suggesting a key role for Tim-3 on macrophages in the development of DN. Furthermore, we found NF-κB activation and TNF-α excretion were upregulated by Tim-3 in diabetic kidneys, and podocyte injury was associated with the Tim-3-mediated activation of the NF-κB/TNF-α signaling pathway in DN macrophages both in vivo and in vitro . Conclusions These results suggest that Tim-3 functions as a key regulator in renal inflammatory processes and serves as a potential therapeutic target for renal injury in DN.

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Novel coronavirus (COVID-19) can lead to multiple organ injuries such as acute respiratory distress syndrome (ARDS), acute renal injury (AKI) and so on. ACE2 is an important part of the renin-angiotensin system (RAS) and a key protein needed for COVID-19 to invade cells. First of all, we searched the HPA, GTEx and FANTOM5 Databases and found that the expression of ACE2 in kidney tissue was significantly higher than that in lung tissue. Then, by searching the Nephroseq Database, it is further verified that ACE2 is highly expressed in renal tissue and plays a protective role in renal tissue. However, current studies have found that the incidence of AKI caused by COVID-19 is much lower than that of ARDS. Because of this, we further searched the proteins interacting with ACE2 protein through the STING Database and analyzed the expression of tissue protein mRNA in the HPA Database. It was noted that AGTR2 mRNA was highly expressed in lung tissue, but low in kidney tissue, and hard tissue specificity in lung tissue. Through further research, it is found that AGTR2 plays a major role in the development of pulmonary fibrosis. Therefore, AGTR2 may be a key protein in COVID-19 pneumonia, and AGTR2 may be a potential new therapeutic target for the treatment of COVID-19 patients.

The present results indicated that there was injury of podocytes in hypertensive nephropathy, which can be ameliorated by calcitriol in SHR, but there was no significant anti-hypertensive effect. Vitamin D/VDR decreased proteinuria perhaps by increasing expression of nephrin and WT1 protein in podocyte of SHRs.