【Animal modeling】-The expression significance of c-Myc, RhoA and YAP in chronic kidney disease induced by the expression of adenosine

  Objective To observe the expressions of renal c-Myc, RhoA and YAP proteins in adenine-induced chronic kidney disease model in rats and their relationship with tubulointerstitial fibrosis.

  Methods Thirty rats were randomly divided into control group (Con group) and model group (CKD group, CKD rat model induced by adenine gavage), and the rats were sacrificed at the 4th, 6th, and 8th weeks, respectively. The renal function and 24h urine protein levels of the rats in the two groups were detected; HE staining was used to observe the renal pathological changes and the degree of renal interstitial injury was scored; Sirius red staining was used to observe the condition of renal tubulointerstitial fibers and judge the degree of fibrosis; immunohistochemical staining was used to observe the degree of fibrosis. The expression of c-Myc, RhoA and YAP protein in kidney tissue; RT-PCR detection of rat kidney c-Myc, RhoA, YAP and Vimentin, Col1, α-SMA mRNA levels, analysis of c-Myc, RhoA and YAP expression level Relationship with tubulointerstitial fibrosis.

  Results Compared with the Con group, the renal function and 24h urinary protein level of the CKD group were significantly increased at each time point (P<0.05). HE staining showed that the renal tubules in the renal tissue were significantly expanded, and Sirius red staining showed collagen in the renal interstitium. Fiber increased significantly. Immunohistochemistry showed that the expressions of c-Myc, RhoA, YAP, Col1 and α-SMA proteins in the renal tubules of the CKD group were significantly higher than those of the Con group at each time point (P<0.05). c-Myc, RhoA, YAP mRNA levels were positively correlated with Col1 mRNA (r=0.927 P=0.001; r=0.988 P=0.001; r=0.745 P=0.013) and α-SMA mRNA expression (r=0.988; P=0.001; r=0.818; P=0.004; r=0.770 P=0.009). In addition, c-Myc and RhoA mRNA, RhoA and YAP mRNA were also significantly positively correlated (r=0.721 P=0.019; r=0.661 P=0.038).

  Conclusion In adenine-induced rat tubulointerstitial fibrosis model, c-Myc, RhoA and YAP are highly expressed and are closely related to the degree of tubulointerstitial fibrosis.