[Leptin induces human lung fibroblast to trans-differentiate into myofibroblast]

To explore the effect of leptin on the transdifferentiation of human lung fibroblast to myofibroblast and its mechanism.

Human embryonic lung fibroblasts (HFL-1) were cultured in vitro and treated with 50, 100, 200 ng/mL recombinant human leptin (rHL) alone or in combination with 5 ng/mL transforming growth factor-β1 (TGF-β1). The protein levels of α-smooth muscle actin (α-SMA), total protein kinase B (AKT) and phosphorylated AKT (p-AKT) in HFL-1 were detected by Western blotting. The proliferation activity of HFL-1 was evaluated by the cell counting kit-8 (CCK-8). The level of collagen type 1 in supernatant fluid of HFL-1 was detected by ELISA.

After treatment with 50, 100 and 200 ng/mL rHL for 48 hours, α-SMA protein expression in HFL-1 was significantly raised as compared with control group. Co-stimulation with 200 ng/mL rHL and 5 ng/mL TGF-β1 increased α-SMA protein expression in HFL-1 remarkably as compared with the treatment with 200 ng/mL rHL or 5 ng/mL TGF-β1 alone. Leptin promoted the expression of p-AKT in HFL-1, and this effect was blocked by PI3K inhibitor LY294002. There was no significant difference in cell viability between HFL-1 treated with 12.5, 25, 50, 100 and 200 ng/mL rHL and without rHL. After treatment with 50, 100 and 200 ng/mL rHL for 48 hours, the level of collagen type 1 in supernatant fluid of HFL-1 significantly increased as compared with control group.

Leptin can induce human lung fibroblast to differentiate into myofibroblast and its mechanism is related to the activation of PI3K/AKT signaling.