Previous studies showed that the decrease in the expression of phosphatase and tensin homolog deleted on chromosome 10 (PTEN) was closely related to the aggravation of DN, but no published study showed how PTEN participated in the regulation of EMT and TIF.
Compared with the NC group, expressions of miR-192 and miR-200b were increased, whereas their target proteins (ZEB2 and PTEN) were reduced in the kidneys of DN mice, which further modulated the expression of their downstream proteins PI3K p85<i>α</i>, P-AKT, P-smad3, and COL4 <i>α</i>1; these proteins were increased in the kidneys of DN mice.
Autophagy was decreased in the progression of renal fibrosis in diabetic nephropathy mice (in vivo) and in high glucose-induced NRK-52E cells (rat kidney epithelial cells) (in vitro) as the expression ofLC-3I and LC-3II (indicators of autophagy) were decreased mice MiR-142-5p was unregulated and PTEN was down-regulated in kidney mice and high glucose-induced NRK-52E cells.
In conclusion, we demonstrated that triptolide ameliorates renal EMT via the PI3K/AKT signaling pathway through the interaction between miR-188-5p and PTEN, indicating that miR-188-5p may be a therapeutic target of triptolide in DKD.
Phosphatase and tensin homolog deleted on chromosome 10 (PTEN) has proven to be downregulated in podocytes challenged with high glucose (HG), and knockout of PTEN in podocytes aggravated the progression of diabetic kidney disease (DKD).
Expression of PTP1B, SHP-1, phosphatase and tensin homolog and SHIP2 are potential mechanisms of podocytes insulin resistance in diabetic kidney disease.
Therefore, our findings indicated that miR-22 may promote TIF by suppressing autophagy partially via targeting PTEN and represents a novel and promising therapeutic target for DN.
These findings indicate that TP alleviates fibrosis by restoring autophagy through the miR-141-3p/PTEN/Akt/mTOR pathway and is a novel therapeutic option for DKD.
Together, this study manifests that miR-217inhibition can protectively antagonize HG-induced podocyte damage and insulin resistance by restoring the defective autophagy pathway via targeting PTEN, representing a novel and promising therapeutic target against diabetic nephropathy.
Relevance of insulin-like growth factor 2 in the etiopathophysiology of diabetic nephropathy: possible roles of phosphatase and tensin homolog on chromosome 10 and secreted protein acidic and rich in cysteine as regulators of repair.