Autophagy plays a role in FSTL1-induced epithelial mesenchymal transition and airway remodeling in asthma

Abstract

Asthma is a chronic disease related to airway hyperresponsiveness and airway remodeling. Airway remodeling is the important reason of refractory asthma and is associated with differentiation of airway epithelia into myofibroblasts via epithelial-mesenchymal transition (EMT) to increase the process of subepithelial fibrosis. There is growing evidence that autophagy modulates remodeling. However, the underlying molecular mechanisms of these effects are still unclear. In this study, we hypothesized that Follistatin-like 1 (FSTL1) promotes EMT and airway remodeling by intensifying autophagy. With the use of transmission electron microscopy (TEM), double-membrane autophagosomes were detected in the airways of patients and mice. More autophagosomes were in patients with asthma and OVA-challenged mice compared with healthy controls. The expression of FSTL1 and beclin-1 was upregulated in the airways of patients with asthma and OVA-challenged mice, accompanied by airway EMT and remodeling. In OVA-challenged mice, the degree of airway remodeling and autophagy was decreased compared with control mice. The effects of FSTL1 on autophagy and EMT were also tested in 16HBE cells in vitro. Additionally, inhibition of autophagy by using LY-294002 and siRNA-ATG5 reduced the FSTL1-induced EMT in 16HBE cells, as measured by E-cadherin, N-cadherin, and vimentin expression. In line herewith, administration of LY-294002 reduced the expression of autophagy, EMT, and airway remodeling markers in FSTL1-challenged WT mice. Taken together, our study suggests that FSTL1 may induce EMT and airway remodeling by activating autophagy. These findings may provide novel avenues for therapeutic research targeting the autophagy and FSTL1 pathway, which may be beneficial to patients with refractory asthma.

Chrysophanol attenuates airway inflammation and remodeling through nuclear factor‐kappa B signaling pathway in asthma

“…It has been reported that the autophagic markers including LC3, Atg 5, and/or Beclin 1 were upregulated in the airway of both patients with asthma and OVA‐challenged mice (T. Liu et al, ). By double staining the mouse lung tissues with LC3B and α‐SMA antibodies, we further noted that the expression of LC3B was markedly upregulated in these α‐SMA‐positive cells in asthmatic mice.…”

“…In addition to alleviating airway inflammation and remodeling, CHR also inhibited autophagy: LC3, Atg 5, and Beclin 1 were decreased. Because inhibition OVA‐induced autophagy can mitigate asthmatic inflammation and airway remodeling (T. Liu et al, ), it is plausible to propose that autophagy inhibition is involved in the antiasthmatic effects of CHR.…”

“…Airway inflammation involves the induction of autophagy (Yin et al, ). Blockade of autophagy was demonstrated to attenuate asthmatic inflammation and airway remodeling (T. Liu et al, ). Antiasthma effects of CHR have been reported by C. Zhang et al ().…”

MicroRNA-144-3p Inhibits Tumorigenesis of Oral Squamous Cell Carcinoma by downregulating ERO1L

“…International Publisher including breast cancer, glioblastoma, hepatocellular carcinoma, and et al [9][10][11]. However, the biological role and clinical significance of miR-144-3p in OSCC are still not known.…”

CTNNAL1 inhibits ozone‐induced epithelial–mesenchymal transition in human bronchial epithelial cells

“…A cycle of persistent airway epithelial damage, improper repair and hyperactive epithelial–mesenchymal transition (EMT) in bronchial epithelial cells has been previously reported to contribute to the pathogenesis of airway inflammation and airway remodelling, which are thought to be the key factors most closely associated with the incidence and prognosis of asthma. In some cases of asthma, the bronchial epithelial cells may undergo EMT and play a pivotal role in subepithelial myofibroblast recruitment and airway inflammation (Hackett et al., , ; Heijink, Postma, Noordhoek, Broekema, & Kapus, ; Liu et al., ). Therefore, clarifying the events of EMT in bronchial epithelial cells in response to harmful stresses may provide insights for improving therapeutic options for asthma.…”