FGF4 alleviates the lung cell damage caused by high glucose via AMPK‑PGC‑1 signaling axis <i>in vitro</i> and <i>in vivo</i>

Long‑term hyperglycemia can damage the capillaries and neural regulation of the lungs, leading to pulmonary microvascular disease and neural regulation disorders, causing abnormalities in lung structure and function. The present study explored the effect of fibroblast growth factor (FGF)4 as a potential therapeutic growth factor on the effect of hyperglycemia on the lungs <i>in vitro</i> and <i>in vivo</i> models. The effect of FGF4 on the damage of lung cells caused by high glucose was evaluated <i>in vitro</i> and <i>in vivo</i> by a series of biochemical experiments (indirect immunofluorescence, western blotting, immunohistochemistry and siRNA). The results showed that FGF4 could effectively alleviate the inhibition of lung cell proliferation caused by high glucose. Further experiments found that high glucose caused inflammation, oxidative stress and fibrosis of lung cells, while the above pathological reactions were alleviated after treatment with FGF4. Further mechanism research showed that FGF4 treatment could markedly improve the survival rate of lung cells, reduce cell death and inflammatory responses and enhance the antioxidant stress resistance of cells. These effects are achieved by activating the adenosine monophosphate (AMP)‑activated protein kinase (AMPK)‑peroxisome proliferator‑activated receptor coactivator 1 (PGC‑1) signaling axis, which plays an important role in regulating cellular metabolism, antioxidant stress and anti‑inflammatory responses. <i>In vivo</i> experiments further confirmed the mitigating effect of FGF4 on lung tissue damage caused by high glucose. FGF4 treatment to diabetic model animals, lung function can be markedly improved and the degree of lung inflammation and fibrosis can be reduced. In summary, FGF4 exhibits a significant mitigating effect on high‑glucose‑induced lung cell damage through the AMPK‑PGC‑1 signaling axis, providing a new strategy for the treatment of diabetes and its pulmonary complications.