Muc5ac Production Inhibited by Decreased lncRNA H19 via PI3K/Akt/NF-kB in Asthma

Abstract

Introduction LncRNAs play important roles in multiple diseases including asthma, while there are a few reports on the role of lncRNA H19 about asthma. This study aimed to investigate the roles and mechanisms of lncRNA H19 in asthma. Methods We detected lncRNA H19 and Muc5ac mRNA by establishing a murine asthma model and an in vitro inflammation model. Regulatory roles of lncRNA H19 in asthma were explored by lncRNA H19 overexpression or knockdown in vitro. To study its mechanisms, we detect p-NF-κB and p-Akt expression, and treated 16-HBE cells with inhibitors of PI3K. To study regulatory effects of miR-675-3p on Muc5ac, miR-675-3p mimics and inhibitors were respectively transfected into 16-HBE cells. Results Firstly, we established a murine asthma model and an in vitro inflammation model. We found that lncRNA H19 expression was decreased, while Muc5ac mRNA was increased in lung tissues of murine asthma model and in the in vitro inflammation model. lncRNA H19 overexpression increased Muc5ac mRNA expression and lncRNA H19 knockdown decreased Muc5ac mRNA expression in 16-HBE cells. Moreover, lncRNA H19 overexpression further increased Muc5ac expression in TNFα-induced in vitro inflammation model. lncRNA H19 knockdown decreased p-Akt and p-NF-κB expression. Inhibitors of PI3K abolished Muc5ac induced by lncRNA H19 overexpression. Although miR-675-3p was increased by lncRNA H19 overexpression, it had no regulatory effects on Muc5ac expression. Discussion These results demonstrated that lncRNA H19 positively regulates Muc5ac expression through PI3K/Akt /NF-κB pathway in the in vitro inflammation model. Therefore, this study indicated that decreased lncRNA H19 in asthma might play a protective role relieving mucus overproduction, and lncRNA H19 might be a potential target for asthma treatment.

PTPRH Alleviates Airway Obstruction and Th2 Inflammation in Asthma as a Protective Factor

“…[13][14][15]24 Besides, asthmatic mice showed that targeting EGFR by inhibiting EGFR phosphorylation can reduce smooth muscle and epithelial cell proliferation, reduce collagen deposition and goblet cell proliferation, and improve airway remodeling in asthma. 11,12,29 Multiple stimuli lead to hypersecretion of mucins via EGFR expression and activation, causing goblet cell metaplasia. 11,12 Consistently, our results showed that PTPRH elevated in serum and induced sputum of asthma patients and lung tissue of asthmatic model, and its expression negatively correlated with EGFR and MUC5AC, which suggests that PTPRH inhibits EGFR phosphorylation involved in epithelial damage/repair processes to relieve dysfunction of airway obstruction and inflammation.…”

“…11,12,29 Multiple stimuli lead to hypersecretion of mucins via EGFR expression and activation, causing goblet cell metaplasia. 11,12 Consistently, our results showed that PTPRH elevated in serum and induced sputum of asthma patients and lung tissue of asthmatic model, and its expression negatively correlated with EGFR and MUC5AC, which suggests that PTPRH inhibits EGFR phosphorylation involved in epithelial damage/repair processes to relieve dysfunction of airway obstruction and inflammation.…”

“…11 Growing evidence has demonstrated that multiple stimuli lead to hypersecretion of mucins (especially MUC5AC/Muc5ac, a marker for goblet cells) via EGFR expression and activation, causing goblet cell metaplasia by cell differentiation. 11,12 PTPRH has been reported to inhibit EGFR activity directly in response to ligandmediated stimulation and is considered a prognostic factor in cancer patients treated with EGFR-targeted monoclonal antibodies. [13][14][15] Recent studies have shown that EGFR expression is significantly increased in the bronchial epithelial of asthma, while ERK1/2 and AKT are also activated as downstream signaling molecules of EGFR.…”

“…[13][14][15] Recent studies have shown that EGFR expression is significantly increased in the bronchial epithelial of asthma, while ERK1/2 and AKT are also activated as downstream signaling molecules of EGFR. 12,16 The EGFR/ERK1/2/AKT signaling pathway is a critical signaling pathway in the pathogenesis of asthma, and the levels have been shown to be consistently increased in both human asthma and in animal models of asthma, especially in T-helper2 (Th2) cellmediated airway inflammation. [16][17][18] However, the function of PTPRH in asthma is unknown yet.…”

CST1 promotes the proliferation and migration of PDGF‐BB‐treated airway smooth muscle cells via the PI3K/AKT signaling pathway

“…15,16 Furthermore, several efforts have been dedicated to revealing the critical effects of the PI3K/AKT signaling pathway in airway remodeling, thereby promoting asthma progression. [17][18][19] In an instance, the authors demonstrated that inhibiting the abnormal upregulation of the PI3K/AKT signaling pathway could reduce the significant infiltration of inflammatory cells and airway remodeling, as well as improve lung function. 19 Nonetheless, it is uncertain regarding the participation of CST1 in the progression of asthma by the PI3K/AKT signaling pathway.…”