[Protective effects of polydatin on HK-2 cells against oxygen-glucose deprivation/re-oxygenation-induced injury by regulating Sonic hedgehog through PI3K/Akt signaling pathway].

OBJECTIVE

To explore the effects of polydatin on human kidney tubular epithelial cells (HK-2 cells) with oxygen-glucose deprivation/re-oxygenation (OGD/R)-induced injury and potential mechanisms.

METHODS

HK-2 cells were cultured under normal or OGD/R condition with different drug treatment methods, including 10, 20 and 40 μmol/L polydatin, and 1 μmol/L Wortmannin, a specific phosphatidylinositol 3-kinase (PI3K) inhibitor. MTT assay was used to detect the survival ability of cells in different groups. The contents of tumor necrosis factor α (TNF-α) and interleukine 1β (IL-1β) in supernatant fluids of the cultured cells were examined by ELISA. And Western blotting was performed to determine the protein levels of total Akt (t-Akt), phospho-Akt (p-Akt) and Sonic hedgehog (Shh) in different groups.

RESULTS

Polydatin significantly improved the viability of cells with OGD/R treatment, and apparently inhibited the secretion of TNF-α and IL-1β induced by OGD/R. The inhibition of PI3K/Akt signaling pathway counteracted the anti-inflammation and pro-survival effects of polydatin and blocked the protein expression of Shh in HK-2 cells. The exogenous addition of human recombinant Shh protein not only improved the survival of cells with OGD/R treatment, but also inhibited the inflammation induced by OGD/R in HK-2 cells.

CONCLUSIONS

Polydatin can exert protective effects on HK-2 cells with OGD/R through regulating the PI3K/Akt-dependent Shh pathway.