LncRNA H19 Inhibits Proliferation and Migration of Airway Smooth Muscle Cells Induced by PDGF-BB Through miR-21/PTEN/Akt Axis

Abstract

Background LncRNA H19 expression is down-regulated in patients with asthma. The hyperplasia of airway smooth muscle cells (ASMCs) promotes the development of airway remodeling in asthma. Therefore, we attempted to evaluate the regulatory function of H19 in the proliferation and migration of ASMCs. Methods The expressions of H19 and miR-21 were detected using qRT-PCR. PDGF-BB-induced abnormal proliferation and migration of ASMCs was used as the airway remodeling model in vitro. The expressions of H19 and miR-21 were modified by transfection with pcDNA3.1-H19 and miR-21 mimic, respectively. CCK-8 assay, flow cytometry-based cell cycle analysis was conducted to examine the proliferation ability of ASMCs. The migration ability was measured by transwell assay. Dual-luciferase reporter system was carried out to find the potential relationship between miR-21 and H19 or PTEN. Western blot was conducted to detect the expressions of PCNA, MMP-9, α-SMA, PTEN, and the phosphorylation level of Akt. Results LncRNA-H19 expression was decreased and microRNA-21 expression was increased in serum samples of children with asthma and PDGF-BB-stimulated ASMCs. Overexpression of H19 reduced the proliferation and migration ability of ASMCs with PDGF-BB treatment and these changes were reversed by miR-21 mimic. H19 promoted the protein level of PTEN via sponging miR-21. Overexpression of H19 suppressed miR-21-induced phosphorylation of Akt, and the suppression effect of H19 on phosphorylation of Akt was significantly reduced after transfecting shPTEN in ASMCs. Conclusion In this study, overexpression of H19 suppressed the proliferation and migration of ASMCs induced by PDGF-BB via miR-21/PTEN/Akt axis, which could be a potential biomarker and target for treating hyperplasia of airway smooth muscle cells.

Role of LncRNA H19/miR-93-5p/Orai1 axis in the regulation of human bronchial smooth muscle cell functions and airway remodeling in murine models of asthma

“…Our results demonstrated a role of H19 in the regulation of Orai1 expression and thus proliferation and migration of hBSMCs. Our results are contradictory to another study which showed that H19 inhibited platelet-derived growth factor (PDGF)-induced proliferation and migration of ASMCs [39]. H19 was also found to be decreased in ASMCs from patients with mild asthma when compared to healthy controls [57].…”

“…The interaction between H19 and miR-93-5p was not studied previously, even that H19 has been reported to interact with multiple miRNAs to regulate diverse biological processes. In smooth muscle cells, H19 is shown to interact with miR-Let-7b and upregulate the expression angiotensin II type 1 receptor (AT 1 R) to promote pulmonary artery smooth muscle cell proliferation [17], interact with miR-21 to regulate the proliferation and migration of ASMCs [39], and interact with miR-599 to promote vascular smooth muscle cell proliferation [40]. In skeletal muscle, the only tissue with persistent H19 expression after birth, H19 was found to interact with miR-675-3p and miR-675-5p to promote skeletal muscle differentiation and regeneration [41].…”

Emerging Advances of Non-coding RNAs and Competitive Endogenous RNA Regulatory Networks in Asthma

“…The detection of serum lncRNA KCNQ1OT1 can be used to monitor the occurrence and progression of airway remodeling in childhood asthma, thus providing a new idea and diagnostic tool for asthma therapy. LncRNA H19 overexpression reduces the growth and migration of platelet-derived growth factor-BB(PDGF-BB)-induced ASMCs by acting on miR-21/PTEN/Akt pathway, which can be used as a potential biomarker and therapeutic target for ASMCs proliferation [ 97 ]. The above results suggest that lncRNAs not only directly act on ASMCs, but also indirectly control miRNA target gene expression to regulate the growth and migration of ASMCs by interacting with miRNA.…”

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

“… 14 lncRNA H19 was decreased in airways of asthmatics compared with healthy controls, 16 and lncRNA H19 overexpression was reported to inhibit proliferation and migration of airway smooth muscle cells. 21 However, its roles and mechanisms in airway epithelial cells in asthma are not reported yet.…”

“…[13][14][15] Moreover, lncRNAs involved in airway diseases have also been widely reported. [16][17][18][19][20][21] LncRNAs in peripheral blood are differentially expressed between asthmatic patients and healthy controls, 22 and even between eosinophilic asthmatics and basophilic asthmatics. 23 LncRNA PVT1 was correlated with glucocorticoid resistance in severe asthmatics, and impacted proliferation of airway smooth muscle cells and release of inflammatory factor IL-6, which could be a therapy target for airway remodeling.…”