5/6Nx caused the development of renal interstitial fibrosis, significantly increased plasma cystatin C and creatinine levels and suppressed renal gelatinase/collagenase, matrix metalloproteinase-1 and -13 activities; effects counteracted by linagliptin treatment in wildtype and Glp1r-/- mice.
In addition, positive correlations were identified between serum Bmi-1 levels and serum creatinine, blood urea nitrogen, cystatin C concentration, and the severity of tubulointerstitial fibrosis (r = 0.248, p < 0.001; r = 0.245, p < 0.001; r = 0.273, p < 0.001; r = 0.536, p < 0.001, respectively).
Molecular and morphological studies revealed that renal interstitial fibrosis, phosphorylation of SMAD3 (a key regulator of renal fibrosis), expression of kidney injury molecule-1 and plasma cystatin C were significantly increased in mice fed a HFD, compared with mice fed a LFD.