Moreover, AMI-1 treatment inhibited Smad3 phosphorylation and TGF beta receptor I expression, but prevented Smad7 downregulation both in the kidney following UUO injury and in cultured renal interstitial fibroblasts exposed to TGF beta1.
We found that ETS2 and profibrogenic factors, alpha-smooth muscle actin (α-SMA) and fibronectin (FN), were significantly increased in the unilateral ureteral obstruction (UUO)-induced renal fibrosis model in mice.
The anti-fibrotic effects of resveratrol were assayed in a rat model of unilateral ureteral obstruction (UUO) in vivo and in fibroblasts and tubular epithelial cells (TECs) stimulated by TGF-β1 in vitro.
Moreover, treatment with DHA attenuated the up-regulation of phosphorylation of phosphatidylinositol-3-kinase (PI3K) and protein kinase B (AKT) in UUO model and TGF-β1-induced primary human kidney fibroblasts.
TGF-β1, NO and E-cadherin levels in the UUO group were significantly higher than the sham group and these values were significantly different in treated groups compared to the UUO group.
The pathological changes, collagen deposition, and protein expressions of profibrotic factors (transforming growth factor-β and connective tissue growth factor) and fibrotic markers (α-smooth muscle actin and fibronectin), which were significantly elevated in the kidneys of UUO mice, could be significantly reversed by icariin treatment.
Quercetin reduced the TGF-β1 expression and inhibited the epithelial cell to mesenchymal cell phenotypic switch, as well as ECM deposition in rats with UUO.
The levels of collagen I, fibronectin and α‑smooth muscle actin were increased by UUO in mice or by transforming growth factor (TGF)‑β1 treatment in NRK‑52E cells, and were reduced by ASX administration.
An in vivo study revealed that petA protected against renal inflammation and fibrosis by reducing the infiltration of macrophages, inhibiting the expression of proinflammatory cytokines (interleukin-1β and tumour necrosis factor-α) and reducing extracellular matrix deposition (α-smooth muscle actin, collagen I and fibronectin) in the obstructed kidney of UUO mice; these changes were associated with suppression of Smad3 and NF-κB p65 phosphorylation.
Our findings demonstrated that Klotho significantly ameliorated EndoMT progression by targeting TGF-β1/Smad/Snail1 signaling in UUO mice, which provides the possibility for Klotho-based therapeutic protection against renal fibrosis.
Compared with UUO group, the renal collagen deposition in transplantation group was significantly reduced, and the expressions of α-SMA mRNA and protein were significantly decreased, while the expressions of HGF mRNA and protein were significantly increased, and the expression of FN mRNA was significantly decreased (P<0.001).
PTEN overexpression significantly inhibited TGFβ1- or unilateral ureteral obstruction (UUO)-induced FAK signaling pathway activation both in vitro and in vivo; more importantly, PTEN silence enhanced TGFβ1- or UUO-induced fibrosis, while FAK inhibitor PF567721 significantly reversed the effects of PTEN silence, indicating that PTEN exerted its effects on TGFβ1- and UUO-induced fibrotic development in vitro and in vivo via inhibiting FAK signaling pathway.
Also, pNaKtide significantly reduced the increased expression of 8-iso-prostaglandin F2α, TGF-β1, interleukin-6 and monocyte chemoattractant protein-1 (MCP-1), as well as reduced macrophage infiltration, in UUO animals.
Finally, the accumulation of α-SMA+ myofibroblasts, deposition of collagen IV and expression of pro-fibrotic factors (CTGF, TGF-β1) were not different between WT and Par2-/- UUO mice.
Furthermore, exogenous miR-26a decreased the protein levels of 2 profibrosis proteins, connective tissue growth factor (CTGF) and TGF-β1, in UUO kidney.
A series of experiments showed the EGFR mimotope immunization could ameliorate renal fibrosis, reduce the expressions of fibronectin, α-SMA and collagen I and alleviate the infiltrations of F4/80+ macrophages in UUO model.
Furthermore, hucMSC-CM markedly attenuated the EMT process and proinflammatory cytokines in rats with UUO and TGF-β1-induced NRK-52E cells. hucMSC-CM also inhibited the TLR4/NF-κB signaling pathway in vivo and in vitro.