6 Some studies revealed that lncRNAs are related to the development and progression of DN.
7–9 For example, lncRNA MALAT1 can regulate renal tubular epithelial pyroptosis by modulating miR-23c targeting of ELAVL1 in DN.
10 LncRNA Tug1 can regulate mitochondrial bioenergetics in DN.
3 Moreover, lncRNA PVT1 (PVT1) has been shown to be involved in accelerating the progression of DN by promoting ECM accumulation and increasing expression of fibronectin 1 (FN1).
11 However, the underlying mechanism of PVT1 on diabetic nephropathy remains unclear.
MicroRNAs (miRNAs) are non-coding RNAs with 20–30 nucleotides that can bind to mRNA to regulate its protein expression.
12 Previous reports indicated that miRNA-325-3p can suppress inflammation and fibrosis in the progression of DN.
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A shared Toll for innate immunity
Toll-like receptor 2 (TLR2) is found in various tissues but is best known for its role in the innate immune system of activating sentinel immune cells in response to infection. Using conditional knockout mice, McCoy
et al. found that TLR2 also mediated innate immune signaling within the endothelium. TLR2 in endothelial cells activated proinflammatory signaling that promoted angiogenesis and immune cell recruitment in response to various “danger” signals, such as those produced during infection or tissue damage. Endothelial TLR2 also supported tumor growth in a mouse model of prostate cancer. These findings show that the endothelium contributes to innate immune responses and that TLR2 may be a therapeutic target in cancer (see also the Focus by Mahfoud and Petrova).