Objective To investigate the effect of microRNA-106a-5p/colony stimulating factor 1 (miR-106a-5p/CSF1) axis on podocyte injury induced by lupus nephritis (LN)-immunoglobulin G (LN-IgG).
Methods Real-time fluorescence quantitative polymerase chain reaction (qRT-PCR) and Western blot were used to detect the expressions of miR-106a-5p and CSF1 in the serum of LN patients and healthy volunteers, as well as in podocytes stimulated by negative control (NC)-IgG (isolated from healthy volunteers) or LN-IgG. Dual-luciferase report assay was used to detect the targeting relationship between miR-106a-5p and CSF1. The effects of modified miR-106a-5p or CSF1 expression on podocyte viability, apoptosis, inflammatory response, and autophagy were studied in vivo by using CCK-8 assay, flow cytometry, enzyme-linked immunosorbent assay (ELISA), and Western blot assay respectively.
Results Compared with healthy volunteers, LN patients showed significant low expression of miR-106a-5p and high expression of CSF1 (P < 0.05); miR-106a-5p expression was significantly reduced in LN-IgG induced podocytes, while CSF1 expression was significantly upregulated (P < 0.05). Functional experiments showed that overexpression of miR-106a-5p was able to reverse LN-IgG induced podocyte viability inhibition and apoptosis promotion, inhibit increases of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α), as well as promote podocyte autophagy, and there were significant differences (P < 0.05). CSF1 was a functional target of miR-106a-5p. The experiment results showed that upregulation of CSF1 was able to significantly inhibit miR-106a-5p overexpression-mediated cell viability enhancement, apoptosis inhibition, inflammatory response inhibition, and autophagy enhancement in LN-IgG induced podocytes (P < 0.05).
Conclusion The miR-106a-5p attenuates LN-IgG induced apoptosis, inflammation in podocytes and promotes podocyte autophagy by targeting CSF1, which suggests that miR-106a-5p may be an effective therapeutic target to delay or alleviate LN.
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