Importantly, transgenic rats with high levels of prorenin developed albuminuria, glomerular and tubulointerstitial fibrosis associated with increased expression of transforming growth factor β (TGFβ) 1 (TGFβ1), plasminogen activator inhibitor-1 (PAI-1), collagen, and fibronectin (FN).
We found that in the UUO model, the expression of renalase was markedly downregulated and adenoviral-mediated expression of renalase significantly attenuated renal interstitial fibrosis, as evidenced by the maintenance of E-cadherin expression and suppressed expression of α-smooth muscle actin (α-SMA), fibronectin and collagen-I.
The data show that LDL and ox-LDL stimulate TEC fibronectin gene message and protein synthesis supporting a pathobiological role for these atherogenic lipoproteins in tubulointerstitial fibrosis.
Strikingly, UK383,367 administration ameliorated tubulointerstitial fibrosis as shown by Masson's trichrome staining in line with the blocked expression of collagen type I/III, fibronectin, and α-smooth muscle actin in the kidneys from UUO mice.
The placebo-treated diabetic mice showed significant signs of beginning renal TIF (shown by picrosirius red staining; increased connective tissue growth factor (CTGF), fibronectin and collagen I deposition; upregulated KIM1 expression) together with an increased number of interstitial myofibroblasts (shown by different mesenchymal markers), while kidneys from diabetic mice treated with CERA revealed less TIF and fewer myofibroblasts.