TIPE2 inhibits PDGF-BB-induced phenotype switching in airway smooth muscle cells through the PI3K/Akt signaling pathway

Abstract

Background Childhood asthma is a common respiratory disease characterized by airway inflammation. Tumor necrosis factor-α-induced protein 8-like 2 (TIPE2) has been found to be involved in the progression of asthma. This study aimed to explore the role of TIPE2 in the regulation of airway smooth muscle cells (ASMCs), which are one of the main effector cells in the development of asthma. Materials and methods ASMCs were transfected with pcDNA3.0-TIPE2 or si-TIPE2 for 48 h and then treated with platelet-derived growth factor (PDGF)-BB. Cell proliferation of ASMCs was measured using the MTT assay. Cell migration of ASMCs was determined by a transwell assay. The mRNA expression levels of calponin and smooth muscle protein 22α (SM22α) were measured using qRT-PCR. The levels of TIPE2, calponin, SM22α, PI3K, p-PI3K, Akt, and p-Akt were detected by Western blotting. Results Our results showed that PDGF-BB treatment significantly reduced TIPE2 expression at both the mRNA and protein levels in ASMCs. Overexpression of TIPE2 inhibited PDGF-BB-induced ASMC proliferation and migration. In addition, overexpression of TIPE2 increased the expression of calponin and SM22α in PDGF-BB-stimulated ASMCs. However, an opposite effect was observed with TIPE2 knockdown. Furthermore, TIPE2 overexpression blocked PDGF-BB-induced phosphorylation of PI3K and Akt, whereas the expression of p-PI3K and p-Akt were aggravated by TIPE2 knockdown. Additionally, the effects of TIPE2 overexpression and TIPE2 knockdown were altered by IGF-1 and LY294002 treatments, respectively. Conclusions Our findings demonstrate that TIPE2 inhibits PDGF-BB-induced ASMC proliferation, migration, and phenotype switching via the PI3K/Akt signaling pathway. Thus, TIPE2 may be a potential therapeutic target for the treatment of asthma.

JIB-04, a histone demethylase Jumonji C domain inhibitor, regulates phenotypic switching of vascular smooth muscle cells

“…Zhang et al revealed that serum amyloid A (SAA) induced downregulation of contractile gene expression and upregulation of synthetic gene expression, while a P38 inhibitor reversed the phenotype switching from a contractile phenotype to a synthetic phenotype caused by SAA [ 29 ]. Moreover, AKT activation was identified to promote PDGF-induced phenotype switching in SMCs [ 30 ]. Our results showed that compared with DMSO, JIB-04 facilitated the phenotypic switching of HASMCs from contractile to synthetic by promoting the phosphorylation of AKT, FOXO3A, and P38 in HASMCs.…”

Insights into potential mechanisms of asthma patients with COVID-19: A study based on the gene expression profiling of bronchoalveolar lavage fluid

“…LY294002 can inhibit the expression of MCP-1, IL-6 and IL-8 released by bronchial epithelial cells, promote pulmonary neutrophil apoptosis and reduce the inflammatory response [ 107 ]. LY294002 can inhibit the proliferation, migration and secretion of proinflammatory factors of airway smooth muscle cells to reduce airway hyperresponsiveness and airway inflammation [ 108 ]. Wortmannin selectively inhibits PI3K and affects the signal pathway transduction, leading to reduced iNOS expression and NO production in bronchiole epithelial cells to alleviate airway inflammation and hyperresponsiveness in asthma patients [ 109 ].…”

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

“…25 Previous studies on asthma pathogenesis indicated that PI3K/Akt signaling pathway regulated hyperresponsiveness and inflammation in the airways. 14,[17][18][19][25][26][27][28][29] In some instances, it was demonstrated that the airway smooth muscle remodeling was regulated by PI3K/AKT in asthma. 28 In this study, it was observed from Western blotting analysis that the PI3K/AKT signaling pathway was activated in PDGF-BB-stimulated human ASMCs.…”

“…In this context, previous studies reported that CST1 could substantially promote the proliferation and migration abilities of various tumor cells by regulating the PI3K/AKT signaling pathway in breast and liver cancers 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 17–19 . 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 .…”

“…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.…”