Expression and significance of hepcidin-ferroportin signaling pathway in rats with adenine-induced chronic kidney disease
Objective To observe the expression of hepcidin-ferroportin(FPN)pathway in adenine-induced chronic kidney disease(CKD)rat model and to explore the mechanism of its involvement in renal fibrosis in CKD.Methods A total of 20 6-week-old male SD rats without specific pathogen were selected.The rats were divided into control group and CKD group,with 10 rats in each group,using a simple random method.Rats were sacrificed at the end of the second and sixth weeks after modeling.The levels of serum creatinine(Scr),blood urea nitrogen(BUN)and 24 h urine protein quantification were measured.The pathological changes of rats were observed.The iron content of rat kidney tissue was detected by colorimetric method,and the level of serum hepcidin-25 was detected by enzyme linked immunosorbent assay method in both groups.Immunohistochemistry and reverse transcription-polymerase chain reaction were used to detect the renal protein and mRNA expression of α-smooth muscle actin(α-SMA),collagen type Ⅰ(Col-Ⅰ),FPN1,interleukin-6(IL-6),tumor necrosis factor-α(TNF-α),nuclear factor kappa-B(NF-κB)P65.Results Compared with the control group,the levels of Scr,BUN,and 24 h urine protein quantification were higher in the CKD group at the end of the second and sixth weeks of modeling(P＜0.05).The results of renal tissue staining showed that the CKD group had obvious glomerular structural disorders,tubular dilation,and interstitial collagen fiber deposition.Compared with the control group,the serum hepcidin-25 level and the iron content of kidney tissues in the CKD group were significantly higher,and correlation analysis suggested that both were positively correlated with the renal function of rats(P＜0.05).Compared with the control group,the protein and mRNA expression levels of α-SMA,Col-Ⅰ,HAMP,IL-6,TNF-α,NF-κB P65 were higher(P＜0.05),while FPN1 expression was lower in CKD group at the end of the second and sixth weeks of modeling(P＜0.05).Correlation analysis results showed that HAMP mRNA expression was positively correlated with α-SMA,Col-Ⅰ,IL-6,TNF-α,and NF-κB p65(P＜0.001),which was negatively correlated with FPN1 mRNA expression(P＜0.001).FPN1 mRNA expression was significantly negatively correlated with α-SMA,Col-Ⅰ(P＜0.001).Conclusions Ferroptosis may be present in the adenine-induced rat model of CKD,and it may be involved in the process of renal fibrosis through the interaction of HAMP-FPN signaling pathway with the inflammatory response.Serum hepcidin-25 is expected to be a serological marker for the early diagnosis of CKD.
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