Silencing a disintegrin and metalloproteinase‑33 attenuates the proliferation of vascular smooth muscle cells via PI3K/AKT pathway: Implications in the pathogenesis of airway vascular remodeling

Fang, Yan; Hao, Yanyan; Gong, Xinji; Sun, Hu; Ding, Jianbing; Wang, Jing

doi:10.3892/mmr.2021.12141

Cited by 5 publications

(6 citation statements)

References 38 publications

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“…For example, the expression of a disintegrin and metalloproteinase-33 (ADAM33), which belongs to the ADAM metalloproteinase family, is associated with airway inflammation, hypersensitivity and remodeling in asthmatic patients. Moreover, the silencing of this gene led to proliferation inhibition and induced the apoptosis of human aortic smooth muscle cells [ 10 ]. Matrix metalloproteinases (MMPs) are important in extracellular matrix degradation.…”

Section: Introductionmentioning

confidence: 99%

Does Vitamin D Work Synergistically with Anti-Asthmatic Drugs in Airway Remodeling?

Sobczak¹,

Pawliczak²

2022

IJMS

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Vitamin D is commonly known for its properties of airway remodeling inhibition. Due to this, we decided to analyze the action of calcitriol with anti-asthmatic drugs in airway remodeling. The HFL1 cell line was treated with calcitriol, beclomethasone 17-propionate, montelukast sodium, LTD4 and TGF-β in different combinations. Real-time PCR was used to analyzed the expression of ACTA2, CDH-1, Vimentin, ADAM33, MMP-9 and CysLTR1 on the mRNA level, whereas Western blot was used to analyze gene expression on the protein level. One-way analysis variants, the Kruskal-Wallis test, Student’s t-test or Welch’s t-test were used for statistical analysis. Concerning the results, pre-treatment with calcitriol increased the inhibitory effect of beclomethasone 17-propionate and montelukast sodium on the expression of ACTA2 (p = 0.0072), Vimentin (p = 0.0002) and CysLTR1 (p = 0.0204), and 1,25(OH)2D3 had an influence on the effects of beclomethasone 17-propionate and montelukast sodium and of CDH1 expression (p = 0.0076). On the protein level, pre-treatment with calcitriol with beclomethasone 17-propionate and montelukast sodium treatment decreased ACTA2 expression in comparison to the LT (LTD4 and TGF-β) control group (p = 0.0191). Hence, our study not only confirms that vitamin D may inhibit airway remodeling, but also shows that vitamin D has a synergistic effect with anti-asthmatic drugs.

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Section: Introductionmentioning

confidence: 99%

Does Vitamin D Work Synergistically with Anti-Asthmatic Drugs in Airway Remodeling?

Sobczak¹,

Pawliczak²

2022

IJMS

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“…Our previous data showed that the silencing of the ADAM33 gene inhibited the cell cycle transition of HASMCs from the G0/G1 phase to the S phase, prolonged cell cycle progression, and suppressed cell proliferation [ 11 ]. To clarify the mechanism by which ADAM33 silencing regulated the cell cycle transition of HASMCs, we examined the expression levels of the downstream factors of the PI3K/AKT/mTOR pathway (the transcription factor FOXO1 and the cell cycle regulator cyclin D1) in HASMCs.…”

Section: Resultsmentioning

confidence: 99%

“…Our previous study showed that a lentiviral vector carrying shRNA targeting ADAM33 (LV-ADAM33) effectively silenced the ADAM33 gene in HASMCs [ 11 ]. In this study, HASMCs were transfected with LV-ADAM33 (MOI = 10, 1 × 10 7 TU/mL; the LV-ADAM33 group) or a negative control vector (MOI = 10, 1 × 10 7 TU/mL; the LV-NC group) for 72 h using the HitransG P reagent (cat no.…”

Section: Methodsmentioning

confidence: 99%

“…The in vitro culture of human embryonic lung tissues also has shown that soluble ADAM33 accelerates vascular endothelial differentiation and promotes angiogenesis [ 10 ]. Importantly, our previous study has demonstrated that the silencing of the ADAM33 gene in human aortic smooth muscle cells (HASMCs) inhibits cell proliferation and promotes apoptosis [ 11 ]. However, whether ADAM33 can affect the migration and inflammatory cytokine secretion of VSMCs during airway vascular remodeling remains unknown.…”

Section: Introductionmentioning

confidence: 99%

“…Additionally, activation of PI3K/AKT/mTOR signaling promotes cell cycle progression and induces DNA synthesis in different pathological conditions, such as cancers and pulmonary vascular diseases [ 13 ]. Our previous findings have suggested that ADAM33 may regulate HASMC proliferation and cell cycle progression via PI3K/AKT signaling [ 11 ]. Therefore, in the current study, we investigated the effects of ADAM33 silencing on HASMC migration and inflammatory cytokine secretion.…”

Section: Introductionmentioning

confidence: 99%

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ADAM33 Silencing Inhibits Vascular Smooth Muscle Cell Migration and Regulates Cytokine Secretion in Airway Vascular Remodeling via the PI3K/AKT/mTOR Pathway

Fang

et al. 2022

Canadian Respiratory Journal

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Introduction. Vascular smooth muscle cells (VSMCs) are highly involved in airway vascular remodeling in asthma. Objectives. This study aimed to investigate the mechanisms underlying the effects of a disintegrin and metalloproteinase-33 (ADAM33) gene on the migration capacity and inflammatory cytokine secretion of VSMCs. Methods. Human aortic smooth muscle cells (HASMCs) were transfected with lentiviral vectors carrying short hairpin RNA (shRNA) targeting ADAM33 or negative control vectors. The migration capacity of HASMCs was evaluated by a transwell assay. The levels of secreted inflammatory cytokines were measured using enzyme-linked immunosorbent assay (ELISA) kits. Reverse transcription-quantitative polymerase chain reaction and Western blot assays were performed to detect mRNA and protein expression levels. Results. Silencing of ADAM33 significantly inhibited the migration of HASMCs. The expression of tumor necrosis factor alpha (TNF-α) in the supernatant of HASMCs was decreased, while that of interferon gamma (IFN-γ) was increased after the transfection of shRNA targeting ADAM33. Insufficient ADAM33 expression also suppressed the expression levels of phosphatidylinositol 3-kinase (PI3K), phospho-protein kinase B (AKT), phospho-mammalian target of rapamycin (mTOR), Rho-associated protein kinases, phospho-forkhead box protein O1 (FOXO1), and cyclin D1, but it did not affect the levels of AKT, mTOR, or Rho. Conclusion. Silencing of the ADAM33 gene inhibited HASMC migration and regulated inflammatory cytokine secretion via targeting the PI3K/AKT/mTOR pathway and its downstream signaling. These data contribute to a better understanding of the regulatory mechanisms of airway vascular remodeling in asthma.

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Adamalysins in COVID-19 – Potential mechanisms behind exacerbating the disease

Dias

Cao

Kwok

2022

Biomedicine & Pharmacotherapy

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Silencing a disintegrin and metalloproteinase‑33 attenuates the proliferation of vascular smooth muscle cells via PI3K/AKT pathway: Implications in the pathogenesis of airway vascular remodeling

Cited by 5 publications

References 38 publications

Does Vitamin D Work Synergistically with Anti-Asthmatic Drugs in Airway Remodeling?

Does Vitamin D Work Synergistically with Anti-Asthmatic Drugs in Airway Remodeling?

ADAM33 Silencing Inhibits Vascular Smooth Muscle Cell Migration and Regulates Cytokine Secretion in Airway Vascular Remodeling via the PI3K/AKT/mTOR Pathway

Adamalysins in COVID-19 – Potential mechanisms behind exacerbating the disease

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