scholarly journals MiR-18a Inhibits PI3K/AKT Signaling Pathway to Regulate PDGF BB-Induced Airway Smooth Muscle Cell Proliferation and Phenotypic Transformation

2021 ◽  
pp. 883-892
Author(s):  
W. Yang ◽  
Y. Chen ◽  
C. Huang ◽  
W. Wang ◽  
C. Huang ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Smooth Muscle ◽  
Airway Smooth Muscle ◽  
Airway Remodeling ◽  
Akt Pathway ◽  
Airway Smooth Muscle Cells ◽  
Migration Ability ◽  
Phenotypic Transformation ◽  
And Migration ◽  
Proliferation And Migration

The increased proliferation and migration of airway smooth muscle cells (ASMCs) is a key process in the formation of airway remodeling in asthma. In this study, we focused on the expression of mircoRNA-18a (miR-18a) in airway remodeling in bronchial asthma and its related mechanisms. ASMCs are induced by platelet-derived growth factor BB (PDGF-BB) for in vitro airway remodeling. The expression of miR-18a in sputum of asthmatic patients and healthy volunteers was detected by qRT-PCR. The expression of miR-18a was over-expressed or interfered with in PDGF-BB-treated ASMCs. Cell proliferation, apoptosis and migration were detected by MTT, flow cytometry and Transwell, respectively; the expression of contractile phenotype marker proteins (SM-22α, α-SM-actin, calponin) and key molecules of the phosphatidylinositol 3-kinase (PI3K)/AKT pathway (PI3K, p-PI3K, AKT and p-AKT) in ASMCs were detected by Western blot. The expression of miR-18a was down-regulated in the sputum and PDGF-BB-treated ASMCs of asthma patients. PDGF-BB could promote the proliferation and migration of ASMCs and inhibit their apoptosis; it could also promote the phenotypic transformation of ASMCs and activate the PI3K/AKT pathway. MiR-18a could inhibit the proliferation, migration ability and phenotypic transformation of ASMCs induced by PDGF-BB to a certain extent and alleviate the effect of PDGF-BB in supressing apoptosis, while miR-18a could inhibit the activation of the PI3K/AKT pathway. MiR-18a inhibits PDGF-BB-induced proliferation, migration and phenotypic conversion of ASMCs by inhibiting the PI3K/AKT pathway, thus attenuating airway remodeling in asthma.

scholarly journals MiR-149 attenuates the proliferation and migration of TGF-β1-induced airway smooth muscle cells by targeting TRPM7 and affecting downstream MAPK signal pathway

2020 ◽  
Author(s):  
Zhengyu Zhu ◽  
Liya Zhang ◽  
Ting Jiang ◽  
Yan Qian ◽  
Yun Sun ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Airway Smooth Muscle ◽  
Transforming Growth Factor ◽  
Muscle Cells ◽  
Airway Smooth Muscle Cells ◽  
And Migration ◽  
Tgf Β1 ◽  
Proliferation And Migration

Asthma is considered as a general term for various chronic inflammatory diseases of the respiratory tract. Growing evidences have supported that microRNAs were involved in mediating cell proliferation, migration, and other cellular functions. MiR-149 has been found to take part in the development of various cancers. However, whether miR-149 participated in the proliferation and migration of transforming growth factor beta 1 (TGF-β1)-induced airway smooth muscle cells was still unknown. In this study, the expression level of miR-149 in human airway smooth muscle cells (ASMCs) was decreased after TGF-β1 treatment in vitro. Additionally, the over-expression of miR-149 obviously suppressed proliferation and migration in human ASMCs. Besides, we found that overexpression of miR-149 could inhibit the expression of transient receptor potential melastatin 7 (TRPM7) both in protein and gene levels. Furthermore, we demonstrated that miR-149 could inhibit the cell proliferation and migration in human ASMCs by targeting TRPM7 through modulating mitogen-activated protein kinases (MAPKs) signaling pathway. Taken together, we strongly supported that miR-149 might be a key inhibitor of asthma by targeting TRMP7. Therefore, our finding suggests a promising biomarker for the development of further targeted therapies for asthma.

scholarly journals Recombinant Rat CC10 Protein Inhibits PDGF-Induced Airway Smooth Muscle Cells Proliferation and Migration

2013 ◽  
Vol 2013 ◽  
pp. 1-8 ◽  
Author(s):  
Ying Wei ◽  
Yu-Dong Xu ◽  
Lei-Miao Yin ◽  
Yu Wang ◽  
Jun Ran ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Cyclin D1 ◽  
Airway Smooth Muscle ◽  
Airway Remodeling ◽  
Muscle Cells ◽  
Clara Cell ◽  
Airway Smooth Muscle Cells ◽  
And Migration ◽  
Proliferation And Migration

Abnormal migration and proliferation of airway smooth muscle cells (ASMCs) in the airway cause airway wall thickening, which is strongly related with the development of airway remodeling in asthma. Clara cell 10 kDa protein (CC10), which is secreted by the epithelial clara cells of the pulmonary airways, plays an important role in the regulation of immunological and inflammatory processes. Previous studies suggested that CC10 protein had great protective effects against inflammation in asthma. However, the effects of CC10 protein on ASMCs migration and proliferation in airway remodeling were poorly understood. In this study, we constructed the pET-22b-CC10 recombinant plasmid, induced expression and purified the recombinant rat CC10 protein fromE. coliby Ni2+affinity chromatography and ion exchange chromatography purification. We investigated the effect of recombinant rat CC10 protein on platelet-derived growth factor (PDGF)-BB-induced ASMCs proliferation and migration. Our results demonstrated that the recombinant CC10 protein could inhibit PDGF-BB-induced cell viability, proliferation and migration. Western blot analysis showed that PDGF-BB-induced activation of cyclin D1 was inhibited by CC10. These findings implicated that CC10 could inhibit increased ASMCs proliferation, and migration induced by PDGF-BB, and this suppression effect might be associated with inhibition of cyclin D1 expression, which might offer hope for the future treatment of airway remodeling.

scholarly journals Scopoletin inhibits PDGF-BB-induced proliferation and migration of airway smooth muscle cells by regulating NF-κκB signaling pathway

2022 ◽  
Vol 50 (1) ◽  
pp. 92-98
Author(s):  
Zhongxiang Fan ◽  
Dan Tang ◽  
Qiang Wu ◽  
Qun Huang ◽  
Jie Song ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Signaling Pathway ◽  
Airway Smooth Muscle ◽  
Airway Remodeling ◽  
Muscle Cells ◽  
Chronic Inflammatory Disease ◽  
Migration And Invasion ◽  
Airway Smooth Muscle Cells ◽  
And Migration

Background: Asthma is a common chronic inflammatory disease of the airway, and airway remodeling and the proliferation mechanism of airway smooth muscle cells (ASMCs) is of great significance to combat this disease.Objective: To assess possible effects of scopoletin on asthma and the potential signaling pathway.Materials and methods: ASMCs were treated PDGF-BB and scopoletin and subjected to cell viability detection by CCK-8 assay. Cell migration of ASMCs was determined by a wound closure assay and transwell assay. The protein level of MMP2, MMP9, calponin and α-SMA were measured using western blot. The levels of NF-κB signaling pathway were detected by Western blotting.Results: Scopoletin inhibited proliferation of PDGF-BB - induced ASMCs. Also it suppressed the migration and invasion of PDGF-BB - induced ASMCs. We further showed that Scopoletin regulated phenotypic transition of ASMCs. Mechanically, Scopoletin inhibited proliferation and invasion of ASMCs by regulating NF-κB signaling pathway.Conclusions: We therefore thought Scopoletin could serve as a promising drug for the treatment of asthma.

scholarly journals MicroRNA-145 Involves in the Pathogenesis of Renal Vascular Lesions and May Become a Potential Therapeutic Target in Patients with Juvenile Lupus Nephritis

2019 ◽  
Vol 44 (4) ◽  
pp. 643-655 ◽  
Author(s):  
Zhaomin Cai ◽  
Wei Xiang ◽  
Xiaojie Peng ◽  
Yan Ding ◽  
Wang Liao ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Lupus Nephritis ◽  
Smooth Muscle Actin ◽  
Vascular Lesions ◽  
Alpha Smooth Muscle Actin ◽  
Migration Ability ◽  
Phenotypic Transformation ◽  
And Migration ◽  
Renal Vascular ◽  
Proliferation And Migration

Aims: The current study was conducted with the central objective of investigating the expression of microRNA-145 (miR-145) in renal vascular lesions (RVLs) in juvenile lupus nephritis (JLN) and its possible mechanism. Methods: The clinical data of 49 JLN patients confirmed by renal biopsy were collected and followed by grouping according to the RVLs score after hematoxylin-eosin staining: mild, moderate, and severe groups. In situ hybridization was used to detect the expression of miR-145 in renal vessels which was then being compared among different RVLs groups. Up-LV-miR-145 and LV-miR-NC lentiviral vectors were constructed and transfected into human vascular smooth muscle cells (HVSMCs), respectively. After HVSMCs were treated with 10.0 µg/L platelet-derived growth factor (PDGF)-BB for 24 h, the proliferation, migration, and apoptosis of endothelial cells were detected by MTT, Transwell assay, and flow cytometry, respectively. Western blot was used to detect expression of alpha-smooth muscle actin (α-SM-actin) and osteopontin (OPN). Results: The expression of miR-145 in renal vascular cells was statistically significant. The higher the inner membrane ratio, the lesser the miR-145 expression. After treatment with PDGF-BB, expression of miR-145 in HVSMCs decreased, proliferation and migration ability enhanced, apoptosis decreased, α-SM-actin decreased, and OPN increased. The proliferation and migration ability of HVSMCs in the LV-miR-145 group suppressed, apoptosis enhanced, α-SM-actin increased, and OPN decreased. Conclusions: Our study revealed that miR-145 expression decreased with the increase of vascular damage. miR-145 can inhibit proliferation, migration, and differentiation phenotypic transformation of HVSMCs induced by PDGF-BB. miR-145 may be involved in the pathogenesis of RVLs and may be a new target for treatment of RVLs in lupus nephritis.

Cyclic mechanical strain‐induced proliferation and migration of human airway smooth muscle cells: role of EMMPRIN and MMPs

2005 ◽  
Vol 19 (11) ◽  
pp. 1507-1509 ◽  
Author(s):  
Nadia A. Hasaneen ◽  
Stanley Zucker ◽  
Jian Cao ◽  
Christian Chiarelli ◽  
Reynold A. Panettieri ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Airway Smooth Muscle ◽  
Mechanical Strain ◽  
Muscle Cells ◽  
Airway Smooth Muscle Cells ◽  
Human Airway Smooth Muscle ◽  
And Migration ◽  
Proliferation And Migration

Interleukin-8: novel roles in human airway smooth muscle cell contraction and migration

2006 ◽  
Vol 291 (5) ◽  
pp. C957-C965 ◽  
Author(s):  
Vasanthi Govindaraju ◽  
Marie-Claire Michoud ◽  
Mustafa Al-Chalabi ◽  
Pasquale Ferraro ◽  
William S. Powell ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Airway Smooth Muscle ◽  
Neutralizing Antibodies ◽  
Airway Remodeling ◽  
Fold Increase ◽  
Airway Smooth Muscle Cell ◽  
Interleukin 8 ◽  
Airway Smooth Muscle Cells ◽  
Cell Contraction ◽  
And Migration

In patients with cystic fibrosis (CF) and asthma, elevated levels of interleukin-8 (IL-8) are found in the airways. IL-8 is a CXC chemokine that is a chemoattractant for neutrophils through CXCR1 and CXCR2 G protein-coupled receptors. We hypothesized that IL-8 acts directly on airway smooth muscle cells (ASMC) in a way that may contribute to the enhanced airway responsiveness and airway remodeling observed in CF and asthma. The aim of this study was to determine whether human ASMC (HASMC) express functional IL-8 receptors (CXCR1 and CXCR2) linked to cell contraction and migration. Experiments were conducted on cells harvested from human lung specimens. Real-time PCR and fluorescence-activated cell sorting analysis showed that HASMC expressed mRNA and protein for both CXCR1 and CXCR2. Intracellular Ca2+ concentration ([Ca2+]i) increased from 115 to 170 nM in response to IL-8 (100 nM) and decreased after inhibition of phospholipase C (PLC) with U-73122. On blocking the receptors with specific neutralizing antibodies, changes in [Ca2+]i were abrogated. IL-8 also contracted the HASMC, decreasing the length of cells by 15%, and induced a 2.5-fold increase in migration. These results indicate that HASMC constitutively express functional CXCR1 and CXCR2 that mediate IL-8-triggered Ca2+ release, contraction, and migration. These data suggest a potential role for IL-8 in causing abnormal airway structure and function in asthma and CF.

scholarly journals Midkine Promotes the Proliferation of Airway Smooth Muscle Cells Induced by LPS Through Notch2 Pathway

2021 ◽  
Author(s):  
Qi Feng Huang ◽  
Tang Deng ◽  
Lihua Li ◽  
Jin Qian ◽  
Qi Li ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Signaling Pathway ◽  
Airway Smooth Muscle ◽  
Airway Remodeling ◽  
Muscle Cells ◽  
Control Group ◽  
Airway Smooth Muscle Cells ◽  
Proliferation And Apoptosis

Abstract Background: Airway smooth muscle cells (ASMC) can produce a variety of cytokine during inflammation, causing changes in the components of the extracellular matrix, which are related to airway remodeling. Midkine (MK) can promote the chemotaxis of various inflammatory cells and release inflammatory factors. Whether Notch and Midkine together affect the proliferation and apoptosis of airway smooth muscle cells is unclear.Objective: To study the mechanism of Midkine on LPS-induced acute lung injury caused by airway smooth muscle cells.Methods: Airway smooth muscle cells were cultured in vitro and divided into 5 groups: control group, lipopolysaccharide group (LPS), Non-targeted siRNA group, MKsiRNA group, Notch inhibitor group (LY411575). The cell proliferation level was detected by CCK-8. The apoptosis level was detected by flow cytometry. The changes of cytokine in the Midkine/Notch2 signaling pathway were detected by Westernblot, qPCR and cellular immunofluorescence.Results: Midkine and Notch2 were highly expressed in the LPS group. MKsiRNA can effectively block the expression of Midkine induced by LPS while down-regulating the expression of Notch2. This result is the same as that of Notch inhibitor (LY411575). Exogenous Midkine promoted the proliferation of airway smooth muscle cells and reduced the rate of apoptosis in the LPS group. When the expression of Midkine was blocked, the proliferation of airway smooth muscle cells in the LPS group was significantly reduced, while apoptosis increased. Inhibiting the expression of Notch, the proliferation of airway smooth muscle cells in the LPS group decreased, and apoptosis increased.Conclusions: Midkine/Notch2 signaling pathway plays an important role in regulating airway smooth muscle cell proliferation and apoptosis in airway inflammation.

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