Background and Aims: The peroxisome proliferator-activated receptor-γ
(PPARγ ) agonists have been shown to dampen TGF-β signaling and suppress
miR-130a in VSMCs and also profibrotic miR-21-5p in the kidney. We have
recently demonstrated that pioglitazone ameliorates established renal fibrosis
by suppressing STAT3 and EGR1 [1], but its effect on renal miR-130a has
not been investigated. Thus, we aimed to study how chronic oral pioglitazone
treatment would affect TGF-β–driven renal miRNA dysregulation in mice.
Method: Ten week old male C57Bl6 control (CTL, n = 6) and TGF-β
transgenic mice (TGFb, n = 12, having elevated plasma TGF-β1 level) were
used. CTL mice and half of TGFb mice received regular chow. The second half
of transgenic mice received pioglitazone containing chow (dose: 20mg/kg/day)
for 5 weeks (TGFb+Pio, n = 6), when the kidneys were evaluated.
Results: Untreated TGFb mice had a 4.7-fold and 2.8-fold type I and type
III collagen mRNA overexpression as compared to controls, respectively. This
was accompanied by 3.8-fold pro-fibrotic Egr2 mRNA, 2.9-fold miR-130a, 3.9-
fold miR-199 and 3.3-fold miR-21 overexpression. Chronic treatment with the
PPARγ agonist pioglitazone reduced the expression of both collagen mRNAs
and miRNAs miR-199 and miR-21 to control levels, but miR-130a reached even
lower values than in control kidneys. Interestingly, the expression of miR-200a
(regulated by TGF-beta and known to ameliorate fibrosis) was similar in all
CTL and TGFb groups, regardless of treatment.
Conclusion: Our data indicate that PPARγ agonist pioglitazone not only
attenuates the TGF-β induced miR-21 overexpression, but also the renal
dysregulation of miR-130a and miR-199, supporting its anti-fibrotic effects.
