Progressive pulmonary fibrosis is caused by elevated mechanical tension on alveolar stem cells

Wu, Huijuan; Yu, Yuanyuan; Huang, Huanwei; Hu, Yucheng; Fu, Siling; Wang, Zheng; Shi, Mengting; Xin, Zhao; Yuan, Jing; Li, Jiao; Yang, Xueyi; Bin, Ennan; Wang, Dong; Zhang, Hongbin; Zhang, Jin; Yuan, Chun; Cai, Tao; Dai, Huaping; Chen, Jingyu; Tang, Nan

doi:10.1016/j.cell.2021.01.020

Cited by 53 publications

(72 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…, the association of CD44 with CD147 (a known MMP inducer) may allow for a synergistic relationship where CD44 positions MMPs and mediates CD147 activation. Elevated mechanical tension has been shown to exacerbate pulmonary lung fibrosis following TGF-β1 activation (70). CD44 and CD147 have both been documented to be involved in mecahnotransduction (71).…”

Section: Discussionmentioning

confidence: 99%

CD147 mediates the CD44s-dependent differentiation of myofibroblasts driven by transforming growth factor-β1

Woods¹,

Grigorieva

Midgley

et al. 2021

Journal of Biological Chemistry

View full text Add to dashboard Cite

This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

show abstract

Section: Discussionmentioning

confidence: 99%

CD147 mediates the CD44s-dependent differentiation of myofibroblasts driven by transforming growth factor-β1

Woods¹,

Grigorieva

Midgley

et al. 2021

Journal of Biological Chemistry

View full text Add to dashboard Cite

show abstract

“…TGFβ1 is also an important index of fibrosis and inflammation 28 . Despite this, pulmonary fibrosis of ARDS mice was also detected after MSCs transplantation 29 .…”

Section: Discussionmentioning

confidence: 99%

Overexpression of TGFβ1 in murine mesenchymal stem cells improve the lung inflammation via impacting Treg/Th17 balance in LPS-induced ARDS mice

Chen¹,

Zhang²,

Xie³

et al. 2020

Preprint

View full text Add to dashboard Cite

Background: T helper 17 cells (Th17)/ regulatory T cells (Treg), as subtypes of CD4+T cells, played an important role in the inflammatory response of acute respiratory distress syndrome (ARDS). However, there is still a lack of effective methods to regulate the differentiation balance of Th17/Treg. It was proved that mesenchymal stem cells (MSCs) could regulate the differentiation of CD4+T cells, but the mechanism was still unclear. TGFβ1, as one of the paracrine cytokines of MSCs, could also regulate the differentiation of Th17/Treg but possess low expression in MSCs. Therefore, mouse MSCs (mMSCs)overexpressing TGFβ1 was constructed by lentivirus transfection and intratracheally transplanted into LPS-induced ARDS mice in our study. And the aim of which was to evaluate the therapeutic effects of mMSCs overexpressing TGFβ1 on inflammation and immunoregulationvia impacting Th17/Treg balance inLPS-induced ARDS mice. Methods: mMSCs with TGFβ1 overexpression were constructed using lentiviral vectors. Then mBM-MSCs and mBM-MSC-TGFβ1 (mMSCs overexpressing TGFβ1) were transplanted intratracheally into the ARDS mice induced by lipopolysaccharide. At 3d and 7d after transplantation, mice were sacrificed and the histopathology of lungs was assessed by hematoxylins and eosin staining and lung injury scoring. Homing of the mMSCs were assayed by ex vivooptical imaging. The relative number of Th17 and Treg in the lungs and spleens in mice were detected by FCM. IL-17A and IL-10 in the lungs of mice were analyzed by western blot. Permeability was evaluated by analysing the protein concentration of BALF using ELISA. Alveolar Lung fibrosis was assessed by Masson’s trichrome staining and Ashcroft scoring. The mortality of ARDS mice was followed until 7 days after transplantation. Results: The transduction efficiencies mediated by the lentiviral vectors were 82.3-88.6%. Overexpressing TGF-β1 inhibited the proliferation of mMSCs during day 5-7 (p<0.05), but made no effects on their differentiation or migration (p>0.05). Compared to the LPS+mBM-MSC-NC group, mMSCs overexpressing TGFβ1 engraftment led to improved histopathology of lung tissue in ARDS mice (p<0.05), much more differentiation of mMSCs into Th17 or Treg (p<0.05) and improved permeability of injured lungs (p<0.05). Moreover, IL-17A was also decreased while IL-10 increased in the LPS+mBM-MSC-TGFβ1 group than in the LPS+mBM-MSC-NC group respectively (p<0.05).Finally, mMSCs overexpressing TGFβ1 did not aggravate the fibrosis of lungs in ARDS mice (p>0.05). Conclusion: MSCs overexpressing TGFβ1 could regulate lung inflammation and attenuated lung injuries via modulating the imbalance of Th17/Treg in the lungs of ARDS mice.

show abstract

“…Among these, alveolar type I cells (AT1) and alveolar type II cells (AT2) constitute two major cell populations found in the alveolar epithelium [ 13 ]. During lung injury, AT2 cells behave as adult tissue stem cells and play a critical role in tissue regeneration by differentiating into AT1 cells [ 14 , 15 , 16 , 17 , 18 ]. Notably, despite being the most abundant cells in the alveolar space, AT2 cells only cover ~5% of the total surface due to their unique cuboidal morphology [ 19 ].…”

Section: Alveolar Regenerationmentioning

confidence: 99%

Alveolar Regeneration in COVID-19 Patients: A Network Perspective

Gupta¹,

Srivastava²,

Minocha

et al. 2021

IJMS

View full text Add to dashboard Cite

A viral infection involves entry and replication of viral nucleic acid in a host organism, subsequently leading to biochemical and structural alterations in the host cell. In the case of SARS-CoV-2 viral infection, over-activation of the host immune system may lead to lung damage. Albeit the regeneration and fibrotic repair processes being the two protective host responses, prolonged injury may lead to excessive fibrosis, a pathological state that can result in lung collapse. In this review, we discuss regeneration and fibrosis processes in response to SARS-CoV-2 and provide our viewpoint on the triggering of alveolar regeneration in coronavirus disease 2019 (COVID-19) patients.

show abstract

Progressive pulmonary fibrosis is caused by elevated mechanical tension on alveolar stem cells

Cited by 53 publications

References 0 publications

CD147 mediates the CD44s-dependent differentiation of myofibroblasts driven by transforming growth factor-β1

CD147 mediates the CD44s-dependent differentiation of myofibroblasts driven by transforming growth factor-β1

Overexpression of TGFβ1 in murine mesenchymal stem cells improve the lung inflammation via impacting Treg/Th17 balance in LPS-induced ARDS mice

Alveolar Regeneration in COVID-19 Patients: A Network Perspective

Contact Info

Product

Resources

About