Airway smooth muscle cells from ovalbumin-sensitized mice show increased proliferative response to TGFβ1 due to upregulation of Smad3 and TGFβRII

Shi, Jianting; Chen, Ming; Ouyang, Lihua; Huang, Lixiang; Lin, Xiaoling; Zhang, Wei; Liang, Ruiyun; Lv, Zhiqiang; Liu, Shanying; Jiang, Shanping

doi:10.1080/02770903.2016.1225760

Cited by 9 publications

(10 citation statements)

References 29 publications

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“…However, the association between erK1/2 signaling and Smad2/3 signaling remains unclear. a previous study has reported that during the proliferation of smooth muscle cells, phosphorylation of erK can be decreased following the use of Smad3 inhibitors (47). conversely, Hough et al (48) identified that phosphorylation of ERK can regulate Smad signaling.…”

Section: Discussionmentioning

confidence: 96%

Effect of CD44 on differentiation of human amniotic mesenchymal stem cells into chondrocytes via Smad and ERK signaling pathways

Wang

et al. 2020

Mol Med Report

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cd44 antigen (cd44) is a transmembrane protein found in cell adhesion molecules and is involved in the regulation of various physiological processes in cells. it was hypothesized that cd44 directly affected the chondrogenic differentiation of human amniotic mesenchymal stem cells (haMScs). in the present study, the expression of chondrocyte-associated factors was detected in the absence and presence of the antibody blocker anti-cd44 antibody during the chondrogenic differentiation of haMScs. Following inhibition of cd44 expression, the transcriptional levels of chondrocyte-associated genes SrY-box transcription factor 9, aggrecan and collagen type ii α 1 chain, as well as the production of chondrocyte markers type ii collagen and aggrecan were significantly decreased in haMScs. Further investigation indicated that there was no significant change in total erK1/2 expression following inhibition of cd44 expression; however, phosphorylated (p)-erK1/2 expression was decreased. The expression of p-Smad2/3 was also upregulated following cd44 inhibition. These data indicated that cd44 may affect the differentiation of haMScs into chondrocytes by regulating the Smad2/3 and erK1/2 signaling pathway.

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Section: Discussionmentioning

confidence: 96%

Effect of CD44 on differentiation of human amniotic mesenchymal stem cells into chondrocytes via Smad and ERK signaling pathways

Wang

et al. 2020

Mol Med Report

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“…TGFβ1 is an important cytokine involved in airway remodeling, and is important in EMT ( 25 ). TGFβ1 mediates tissue inflammation in asthma ( 26 ).…”

Section: Resultsmentioning

confidence: 99%

“…There are various hypotheses regarding the role of TGFβ1 in asthma. The majority of studies have shown that TGFβ1 can trigger EMT ( 29 ) and that it is important in the onset of asthma and airway remodelling ( 25 ). TGFβ1 is a remodeling related mediator; additionally, the increased secretion of TGFβ1 induced by asthmatic chronic inflammation may result in EMT, which is one of the most important mechanisms of airway inflammation and airway remodeling in asthma ( 7 ).…”

Section: Discussionmentioning

confidence: 99%

BMS‑345541 inhibits airway inflammation and epithelial‑mesenchymal transition in airway remodeling of asthmatic mice

Zhu

et al. 2018

Int J Mol Med

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The present study aimed to investigate the possible effects and regulatory mechanism of the inhibitor of nuclear factor-κB kinase complex β subunit (IKKβ) inhibitor BMS-345541 on airway inflammation, airway remodeling and epithelial-mesenchymal transition (EMT) in an ovalbumin (OVA) exposure asthma model in mice. The asthma mouse model was generated by sensitization and challenge with OVA. BMS-345541/dimethyl sulfoxide (DMSO) was administered perorally dairy in two therapeutic groups throughout the entire OVA challenge process. At 24 h following the last challenge, airway hyperresponsiveness (AHR) and airway inflammation were examined, and serum, bronchoalveolar lavage fluid (BALF) and lung samples were collected. Lung tissue was stained and assessed for pathological changes. The total number and classification of inflammatory cells in the BALF were examined. Levels of transforming growth factor β1 (TGFβ1) in the serum and BALF were measured using an enzyme-linked immunosorbent assay. The differential expression of EMT regulators E-cadherin and vimentin was detected by immunohistochemical staining, reverse transcription-quantitative polymerase chain reaction analysis and western blot analysis. The results showed that OVA successfully induced allergic asthma. The asthmatic mice had AHR, airway inflammation, airway remodeling, a high expression of TGFβ1, and evidence of EMT. Following BMS-345541 treatment, there was significant inhibition of pathophysiological signs, including increased pulmonary eosinophilia infiltration, mucus hypersecretion and AHR. Treatment with BMS-345541 significantly reduced levels of TGFβ1. In addition, BMS-345541 notably downregulated the expression of vimentin and increased the expression of E-cadherin. These data suggested that the increased secretion of TGFβ1 induced by asthmatic inflammation can lead to EMT, and the IKKβ inhibitor BMS-345541 may alter airway remodeling by preventing EMT in an OVA asthma model. Therefore, IKKβ inhibitors require investigation as potential asthma therapies.

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“…26,27 We have also previously demonstrated that TGF-b1 can stimulate the proliferation of ASMCs in vitro via Smad3 and ERK1/2 signaling. 1 How pulmonary macrophages regulate the development of asthma remains to be fully characterized. CD206-positive M2 macrophages expressing high levels of major histocompatibility complex II have been shown to be significantly increased (2.9-fold) in bronchoalveolar lavage fluid samples from patients with asthma relative to healthy controls.…”

Section: Discussionmentioning

confidence: 99%

“…In individuals affected by asthma, chronic inflammation can result in deleterious airway remodeling characterized by subepithelial fibrosis and by increases in smooth muscle mass, airway wall thickness and mucous gland density. 1,2 This remodeling process is physiologically complex, with a range of different cell types and signaling processes interacting to mediate overall disease pathology.…”

Section: Introductionmentioning

confidence: 99%

miR‐142‐5p and miR‐130a‐3p regulate pulmonary macrophage polarization and asthma airway remodeling

et al. 2020

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Macrophages are key regulators of the development and progression of asthma, facilitating deleterious airway remodeling in affected patients. Immune cell function is tightly regulated by microRNAs (miRNAs), but how these miRNAs impact macrophage-mediated airway remodeling in the context of asthma remains to be determined. In this study, we utilized an ovalbumin (OVA)based murine model of asthma to evaluate the importance of miRNAs within these macrophages. We found that macrophages from mice that had been sensitized with and exposed to OVA expressed higher levels of M2-like phenotypic markers and exhibited significantly altered expression of both miR-142-5p and miR-130a-3p. When these isolated pulmonary macrophages were cultured in vitro, we determined that transfecting them with miR-142-5p antisense oligonucleotide (ASO) or miR-130a-3p mimics was sufficient to inhibit the ability of interleukin-4 to induce M2 cytokine production. We additionally confirmed the in vivo relevance of these miRNAs in a Ccr2 À/À murine model system mimicking asthma. Specifically, we determined that transfecting monocytes with miR-142-5p ASO and/or miR-130a-3p mimics was sufficient to disrupt the ability of these cells to promote airway remodeling. As such, these findings reveal that miR-142-5p and miR-130a-3p dysregulation are important factors governing the polarization of macrophages and associated airway remodeling in OVA-sensitized mice.

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Airway smooth muscle cells from ovalbumin-sensitized mice show increased proliferative response to TGFβ1 due to upregulation of Smad3 and TGFβRII

Abstract: ASMCs isolated from OVA-sensitized mice showed hyper-proliferation upon TGFβ1 stimulation. This might have been associated with up-regulated Smad3 and TGFβRII and mediated by ERK1/2 downstream to Smad3.

Cited by 9 publications

References 29 publications

Effect of CD44 on differentiation of human amniotic mesenchymal stem cells into chondrocytes via Smad and ERK signaling pathways

Effect of CD44 on differentiation of human amniotic mesenchymal stem cells into chondrocytes via Smad and ERK signaling pathways

BMS‑345541 inhibits airway inflammation and epithelial‑mesenchymal transition in airway remodeling of asthmatic mice

miR‐142‐5p and miR‐130a‐3p regulate pulmonary macrophage polarization and asthma airway remodeling

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