Induction of heme oxygenase‐1 antagonizes PM2.5‐induced pulmonary VEGFA expression through regulating HIF‐1α.

Particulate matter (PM) 2.5 has long been regarded as a major risk factor of the respiratory system, which constitutes a threat to human health. Although the positive relationship between PM2.5 exposure and the development of respiratory diseases has been well established, limited studies investigate the intrinsic self‐protection mechanisms against PM2.5‐induced respiratory injuries. Excessive pulmonary inflammation served as a key pathogenic mechanism in PM2.5‐induced airway dysfunction, and we have previously shown that PM2.5 induced the production of vascular endothelial growth factor A (VEGFA) in the bronchial epithelial cells, which subsequently led to pulmonary inflammatory responses. In the current study, we found that PM2.5 also concurrently induced the expression of the stress‐responsive protein heme oxygenase‐1 (HO‐1) along with VEGFA in the bronchial epithelial cells both in vivo and in vitro. Importantly, knocking down of HO‐1 expression significantly increased the synthesis and secretion of VEGFA; while overexpression of HO‐1 showed the opposite effects, indicating that HO‐1 induction can antagonize VEGFA production in the bronchial epithelial cells upon PM2.5 exposure. Mechanistically, HO‐1 inhibited PM2.5‐evoked VEGFA induction through modulating hypoxia‐inducible factor 1 alpha (HIF‐1α), which was the upstream transcriptional factor of VEGFA. More specifically, HO‐1 could not only inhibit HIF‐1α expression, but also suppress its transactivity. Taken together, our results suggested that HO‐1 was an intrinsic protective factor against PM2.5‐induced pulmonary VEGFA production with a mechanism relating to HIF‐1α, thus providing a potential treatment strategy against PM2.5 triggered airway injuries. [ABSTRACT FROM AUTHOR]