Enhanced renoprotective effect of GDNF-modified adipose-derived mesenchymal stem cells on renal interstitial fibrosis

Abstract Background The therapeutic effect of mesenchymal stem cells (MSCs) from human adipose tissue on renal interstitial fibrosis has been demonstrated by several groups. However, the way to enhance renoprotective adipose-derived (AMSCs) and possible mechanisms are still unclear. present study aimed determine whether glial cell line-derived neurotrophic factor (GDNF)-modified AMSCs hold an enhanced protective fibrosis. Methods were isolated purified for culture. gene GDNF constructed transfect into AMSCs. ability GFP-AMSCs GDNF-AMSCs supernatants promote tube formation endothelial cells, repair damaged junctions, improve function was compared using assay, immunofluorescence techniques, vascular ring respectively. Furthermore, HE Masson staining used observe histological morphology kidney in vivo. Peritubular capillary changes detected analyzed fluorescence microangiography (FMA). Meanwhile, hypoxia, oxidative stress, fibrotic markers, PI3K/Akt pathway proteins measured western blot or qRT-PCR technics. Results Compared with only, could injured angiogenesis through secreting more growth factors supernatant GDNF-AMSC culture media vitro studies. Studies vivo, unilateral ureteral obstruction (UUO)-induced mice injected transfected their tail veins. We showed that homing observed group GFP-AMSC group. animals treated exhibited improvement rarefaction induced obstructed we reported protect tissues against microvascular injuries via activation signaling pathway. Therefore, further ameliorated suppressed finally inhibited transition noting decreased coexpression (CD31) myofibroblast (a-SMA) markers. Conclusion Collectively, our data indicated enhances improving microcirculation PI3K/Akt/eNOS afterward inhibit EndMT process fibrogenesis, which should have a vast implications designing future remedies chronic disease (CKD) treatment.