To analyze the effect of the Notch signaling pathway on the number and function of peripheral blood Th17 cells in the process of renal interstitial fibrosis of rats with IgA nephropathy.

The rats were divided into the blank group and the model group. When the model was established, the model group was randomly divided into 3 sub-groups: the dimethyl sulfoxide (DMSO) group (for Notch signaling pathway activating), TGF-β group, and DAPT group (for Notch signaling pathway inhibiting). After the peripheral blood mononuclear cells (PBMC) were separated with lymphocyte isolation solution, they were treated with DMSO (0.1%), TGF-β inhibitor (2.5 μmol/L), and DAPT (2.5 μmol/L), respectively. The kidney tissues of the rats were collected, and the IgA deposition in the rat kidneys was observed by immunofluorescence method. The expressions of Notch1, Hes1, Hes5, TGF-β, and Smad3 genes in both the kidneys and the PBMC was detected with RT-PCR method. Flow cytometry was used to detect Th17 and Treg cells in the blood, while ELISA method was used to detect the levels of IL-23, IL-17, IL-10, and TGF-β1 in the supernatant of PBMC culture of the groups.

The expressions of Notch1, Hes1, Hes5, TGF-β, and Smad3 genes in the model groups were significantly higher than those in the blank group (P<0.05). The expressions of Notch1, Hes1, Hes5, TGF-β, and Smad3 genes as well as PBMC level of phosphorylated Smad3 protein in the DAPT group and TGF-β group were significantly lower than those in the DMSO group (P<0.05). Besides, the Th17 cells, Treg cells, and Th17/Treg ratios of TGF-β group and DAPT group were also lower than those of DMSO group (P<0.05). The levels of IL-17, IL-23, TGF-β, and IL-10 in the culture supernatant of the DAPT group and TGF-β group were all lower than those of the DMSO group (P<0.05). The IL-10 level of the DAPT group was significantly higher than that of the TGF-β group (P< 0.05).

In the process of renal interstitial fibrosis of the rats with IgA nephropathy, the Notch signaling pathway was abnormally activated. The Notch signaling pathway could not only affect the number of Th17 cells in the peripheral blood, but also had a certain regulatory effect on their function.