Journal of Shandong University (Health Sciences) ›› 2021, Vol. 59 ›› Issue (3): 18-25.doi: 10.6040/j.issn.1671-7554.0.2020.1135

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Effect of miR-203-3p targeted TREM1 gene on the regulation of TGF-β1/p38MAPK signaling pathway on the proliferation and apoptosis of renal tubular epithelial cells in lupus nephritis mice

LUO Huichen1, HU Danhui2, ZHANG Ji3   

  1. 1.Department of Division of Rheumatology;
    2. Deparment of Neonatology;
    3. Rheumatism Laboratory, The First Affiliated Hospital of University of South China, Hengyang 421001, Hunan, China
  • Published:2021-04-06

Abstract: Objective To investigate the effect of miR-203-3p on proliferation and apoptosis of renal tubular epithelial cells in lupus nephritis(LN)mice and its possible molecular mechanism. Methods Spontaneous LN mice(LN group)and wild-type C57BL/6 mice(NC group)were selected, 8 in each group, and the expression of miR-203-3p and triggering receptor expressed on myeloid cells-1(TREM1)protein in renal tissue were detected by qRT-PCR and Western blotting, respectively. The renal tubular epithelial cells of LN mice were isolated and transfected with miR-203-3p mimic and its negative control(miR-NC), then the expression of miR-203-3p in transfected renal tubular epithelial cells was detected by qRT-PCR; cell proliferation and apoptosis were detected by CCK-8 and flow cytometry; the levels of inflammatory factors TNF-α, IL-1β and IL-6 were detected by ELISA; the proteins expressions of TREM1, Bax, Bcl-2, TGF-β1, p-p38MAPK and p38MAPK were evaluated by Western blotting; the target relationship between miR-203-3p and TREM1 was assessed by dual luciferase reporter gene assay. Results Compared with NC group mice, the expression level of miR-203-3p in renal tissue of LN mice was significantly decreased(P<0.001), while the expression of TREM1 protein was significantly increased(P<0.001). Overexpression of miR-203-3p markedly inhibited the expression of TREM1 protein in renal tubular epithelial cells of LN mice(F=366.230, P<0.001), and the dual luciferase reporter gene experiment confirmed that TREM1 was the target gene of miR-203-3p. In addition, overexpression of miR-203-3p significantly inhibited the levels of TNF-α, IL-1β and IL-6 in tubule epithelial cells of LN mice(all P<0.01), promoted the cell proliferation(F24 h=14.841, F48 h=21.701, F72 h=29.893, P<0.001), inhibited its apoptosis(F=238.700, P<0.001), and up-regulated the expression of Bcl-2 protein(F=371.820, P<0.001), while down-regulated the proteins expression of Bax, TGF-β1 and p-p38MAPK(FBax=225.640, FTGF-β1=27.090, Fp-p38MAPK=103.250, P<0.001). Conclusion miR-203-3p can promote the proliferation and inhibit apoptosis of LN mice glomerular epithelial cells by targeting the down-regulation of TREM1 protein expression, which may be related to inhibition of TGF-β1/p38MAPK signaling pathway.

Key words: Lupus nephritis, miR-203-3p, Triggering receptor expressed on myeloid cells-1, TGF-β1/p38MAPK signaling pathway

CLC Number: 

  • R3
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