Purpose: The purpose of this study is to assess the potential effects of metformin on the development of EMT and tubulointerstitial fibrosis 12 weeks after acute renal ischemia-reperfusion.
Methods: Male Sprague-Dawley rats were randomly assigned to four groups: Sham, IRI, transient administration of metformin (TAM), and continuous administration of metformin (CAM). Metformin was administered i.p. at a dose of 125 μg kg (- 1) d( - 1) 3 d prior to suffering from IRI (TAM), or from 3 d before suffering from IRI to 12 weeks after reperfusion (CAM). Renal function, histology, and expressions of IL-6, TNF-α, α-SMA, TGF-β1, Vimentin, and E-cadherin were analyzed.
Results: Tubulointerstitial fibrosis worsened further in IRI, accompanied by the increased expressions of interleukin-6, TNF-α, α-SMA, TGF-β1, Vimentin, and loss of E-cadherin. Although there were no significant differences between IRI and TAM (p > 0.05). Compared with the IRI, expressions of IL-6, TNF-α, α-SMA, TGF-β1, and Vimentin were reduced and the expression of E-cadherin was restored in CAM (p < 0.05). CAM also significantly promoted activation of AMPK (p < 0.05), which showed no difference among Sham, IRI, and TAM (p > 0.05).
Conclusions: CAM significantly attenuated tubulointerstitial fibrosis and EMT in rats, potentially via activation of AMPK and down-regulation of TGF-β1.
Keywords: Epithelial matrix transformation; fibrosis; ischemia–reperfusion injury; metformin; renal.