Backgrounds: Vocal fold fibrosis, resulting from injury, leads to irreversible impairments in voice, swallowing, and respiration, with serious consequences. The AMPK signaling pathway plays a crucial role in the development of fibrosis. This article reviews the potential of AMPK activators, such as aldometanib, in treating and preventing vocal fold fibrosis
Methods: For the in vitro experiments, human vocal fold fibroblasts were differentiated into myofibroblasts by treatment with TGF-β. These activated cells were then subjected to various concentrations of aldometanib. Cell viability was assessed using the CCK-8 assay.Apoptosis was analyzed by flow cytometry.The mRNA and protein expression levels of genes associated with the JAK2-STAT3 pathway were measured via RT-PCR and Western blot analysis, respectively.For the in vivo validation, a vocal fold scar model was established in rats. The anti-fibrotic efficacy of [Please confirm and replace "fasting essence"] was evaluated through Alcian blue and EVG staining of the injured vocal folds.
Results: Aldometanib significantly suppressed TGF-β-induced fibroblast proliferation and migration, without inducing apoptosis. Furthermore, it inhibited fibroblast activation by targeting the JAK2-STAT3 pathway. Ultimately, Aldometanib mitigated vocal fold fibrosis by ameliorating extracellular matrix (ECM) disorders, characterized by reduced HA over-accumulation and restored elastic and collagen fiber deposition.
Conclusion: The inhibition of the JAK2-STAT3 pathway by aldometanib underlies its therapeutic effect on vocal fold fibrosis.
Keywords: AMPK activator; Vocal fold scar; Vocal fold fibrosis; Fibroblast