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(F_{24 h}=14.841, F_{48 h}=21.701, F_{72 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(F_Bax=225.640, F_TGF-β1=27.090, F_p-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