Downregulated Rac1 promotes apoptosis and inhibits the clearance of apoptotic cells in airway epithelial cells, which may be associated with airway hyper‐responsiveness in asthma

Abstract

The accumulation of airway apoptotic cells may be an important factor causing airway hyper-responsiveness (AHR). Whether the apoptotic cells can be promptly removed is related to the occurrence and course of asthma. In recent years, studies have shown that Rac1 is involved in many cellular biological activities including the formation and elimination of apoptotic cells. In this study, based on the analysis of airway local cells and related factors in asthmatic mice, we evaluated the expression of Rac1 in airway epithelial cells or phagocytes and analysed its relationship with the incidence of apoptosis or scavenging of apoptotic cells. Our data showed that the expression level of Rac1 in asthmatic mice decreased significantly, while the expression of IL-33 increased obviously. The airway epithelial cell line was stimulated by curcumin at 50 μmol/L for 24-48 hours; more than 50% of the cells were apoptotic, and of which, about 20% were late apoptosis. Rac1 inhibitor (NSC23766) can enhance the apoptosis effect. In addition, the ability of phagocytosis and migration in the epithelial cells or macrophages was increased following the application of Rac1 inhibitors or specific siRNA in a dose-dependent manner, and the expression level of IL-33 was simultaneously increased after blocking Rac1. It is suggested that the down regulation of Rac1 in asthma may contribute to the apoptosis of airway epithelial cells and affect the clearance of apoptotic cells, which will lead to the aggregation of the apoptotic cells in the respiratory tract and participate in AHR.

Fructose‐1,6‐bisphosphatase aggravates oxidative stress‐induced apoptosis in asthma by suppressing the Nrf2 pathway

“…Apoptosis is a form of programmed cell death that plays an essential role in lung disease, such as asthma. Elevated levels of apoptosis in bronchial epithelial cells have been reported in patients with childhood asthma 40,41 . Therefore, it is important to investigate the potential mechanism of apoptosis in asthma.…”

“…Elevated levels of apoptosis in bronchial epithelial cells have been reported in patients with childhood asthma. 40,41 Therefore, it is important to investigate the potential mechanism of apoptosis in asthma. Some studies have reported that Fbp1 can promote apoptosis in certain cancers.…”

Rac1, A Potential Target for Tumor Therapy

“…Overexpression of ARHGAP24 significantly inhibits the activities of RhoA and Rac1 and induced apoptosis of lung cancer cells via STAT6-WWP2-p27 axis (74). Rac1 participates in the formation and elimination of apoptotic cells and coordinates receptor signals related to apoptosis and proliferation (75,76). In B-cell lymphoma, Rac1 was found to be a new binding partner of Bcl-2, which can stabilize its antiapoptosis activity (77).…”

Programmed Cell Death in Asthma: Apoptosis, Autophagy, Pyroptosis, Ferroptosis, and Necroptosis

“…[24][25][26][27] Through immunofluorescence staining, Jiangbo Wang et al discovered that the expression of caspase-3 in bronchial epithelial cells of asthma patients increased, and the increase was most evident in samples from patients with severe asthma. 28 Increased apoptosis of airway epithelial cells was also found in asthma mice influenced by OVA, 29 HDM, 30 and the fungal allergen Alternaria alternata. 31 Studies have shown that the increased apoptosis of epithelial cells is a crucial mechanism by which some external factors cause the worsening of asthma.…”