Hypoxia inducible factor 1 subunit alpha mediates autophagy disorder of oral lichen planus by regulating lysosomal pathway.

Oral lichen planus (OLP), known as a common and chronic mucosal inflammatory disease. Due to its potential for cancerous transformation, this disease has long been a subject of significant concern. Its pathogenesis is that an unknown antigen activates oral keratinocytes and antigen-presenting cells (APCs) in the epithelium, leading to a T cell-mediated immune response. This study investigates the regulatory role of HIF-1α transcription factor and the potential role of autophagy in a simulated OLP inflammatory cell model. In this study, by comparing the control group with the model group, we observed a notable up-regulation of HIF1A mRNA expression. Additionally, both the autophagy marker protein LC3-II and its substrate p62 exhibited abnormal accumulation, suggesting that autophagy is impaired at the lysosomal degradation stage. Furthermore, mechanistic studies have shown that HIF-1α leads to dysfunction of the autophagy-lysosomal pathway by inhibiting the expression of lysosomal-related genes, while knockdown of HIF-1α alleviates the disruption of autophagic and promotes the improvement of cell activity. In experiments with C. elegans, stimulation with Porphyromonas gingivalis lipopolysaccharide (P. gingivalis LPS) shortens worms' lifespan, but knocking down the hif-1 gene reverses this effect. Similarly, deletion of the key autophagy genes bec-1 and lgg-1 reduces worm survival rates. Results indicate that HIF-1α plays a vital role in regulating autophagy-lysosomal function and cellular homeostasis. In summary, the excessively high expression of HIF-1α aggravates cellular and systemic damage by impairing autophagy-lysosomal function in OLP. Conversely, the targeted inhibition of HIF-1α restores autophagy function, suggesting a potential therapeutic strategy.