TGFβ mediates collagen production in human CRSsNP nasal mucosa‐derived fibroblasts through Smad2/3‐dependent pathway and CTGF induction and secretion

Shieh, Jiunn‐Min; Chi, Jessie Chao-Yun; Wu, Wen‐Bin

doi:10.1002/jcp.27718

Cited by 22 publications

(19 citation statements)

References 33 publications

(50 reference statements)

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“…Indeed, TGF-β plays a critical role in every stage of RT-induced fibrosis, including its initiation, development, and persistence [75]. As expected, we observed that DEX decreased the level of active TGF-β in irradiated breast adipose tissue at 7 weeks post-RT, and this was accompanied by a decrease in the levels of CTGF, secretion of which is stimulated by TGF-β [76]. So how might ATX-LPA signaling fit into the overall pathway leading to RT-induced breast fibrosis?…”

Section: Discussionsupporting

confidence: 84%

Dexamethasone Attenuates X-Ray-Induced Activation of the Autotaxin-Lysophosphatidate-Inflammatory Cycle in Breast Tissue and Subsequent Breast Fibrosis

Meng

Wuest

Tang

et al. 2020

Cancers

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We recently showed that radiation-induced DNA damage in breast adipose tissue increases autotaxin secretion, production of lysophosphatidate (LPA) and expression of LPA1/2 receptors. We also established that dexamethasone decreases autotaxin production and LPA signaling in non-irradiated adipose tissue. In the present study, we showed that dexamethasone attenuated the radiation-induced increases in autotaxin activity and the concentrations of inflammatory mediators in cultured human adipose tissue. We also exposed a breast fat pad in mice to three daily 7.5 Gy fractions of X-rays. Dexamethasone attenuated radiation-induced increases in autotaxin activity in plasma and mammary adipose tissue and LPA1 receptor levels in adipose tissue after 48 h. DEX treatment during five daily fractions of 7.5 Gy attenuated fibrosis by ~70% in the mammary fat pad and underlying lungs at 7 weeks after radiotherapy. This was accompanied by decreases in CXCL2, active TGF-β1, CTGF and Nrf2 at 7 weeks in adipose tissue of dexamethasone-treated mice. Autotaxin was located at the sites of fibrosis in breast tissue and in the underlying lungs. Consequently, our work supports the premise that increased autotaxin production and lysophosphatidate signaling contribute to radiotherapy-induced breast fibrosis and that dexamethasone attenuated the development of fibrosis in part by blocking this process.

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Section: Discussionsupporting

confidence: 84%

Dexamethasone Attenuates X-Ray-Induced Activation of the Autotaxin-Lysophosphatidate-Inflammatory Cycle in Breast Tissue and Subsequent Breast Fibrosis

Meng

Wuest

Tang

et al. 2020

Cancers

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“…These results indicate that hyperoxia alters the balance in two isoforms of endoglin towards increased S-endoglin and that S-endoglin attenuates TGFβ-ALK1-Smad1/5 signalling but stimulates tGfβ-ALK5-Smad2/3 signalling in pulmonary ECs, which may lead to impaired pulmonary angiogenesis in developing lungs. open Scientific RepoRtS | (2020) 10:3043 | https://doi.org/10.1038/s41598-020-59928-x www.nature.com/scientificreports www.nature.com/scientificreports/ through enhancement of the TGFβ-ALK1-Smad1/5 pathway, while connective tissue growth factor (CTGF) expression increases through enhancement of the TGFβ-ALK5-Smad2/3 pathway [27][28][29][30][31] .Several independent findings have demonstrated that endoglin is engaged in TGFβ receptor complex formation and the modulation of downstream signalling [32][33][34][35] . The expression of two alternatively spliced isoforms, long (L-) endoglin and short (S-) endoglin, has been demonstrated in human and mouse lung tissues in vivo 33,34,36,37 .…”

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confidence: 99%

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confidence: 99%

S-endoglin expression is induced in hyperoxia and contributes to altered pulmonary angiogenesis in bronchopulmonary dysplasia development

Lee

Nam

et al. 2020

Sci Rep

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Altered pulmonary angiogenesis contributes to disrupted alveolarization, which is the main characteristic of bronchopulmonary dysplasia (BPD). Transforming growth factor β (tGfβ) plays an important role during lung vascular development, and recent studies have demonstrated that endoglin is engaged in the modulation of tGfβ downstream signalling. Although there are two different isoforms of endoglin, L-and S-endoglin, little is known about the effect of S-endoglin in developing lungs. We analysed the expression of both L-and S-endoglin in the lung vasculature and its contribution to tGfβ-activin-like kinase (ALK)-Smad signalling with respect to BPD development. Hyperoxia impaired pulmonary angiogenesis accompanied by alveolar simplification in neonatal mouse lungs. S-endoglin, phosphorylated Smad2/3 and connective tissue growth factor levels were significantly increased in hyperoxia-exposed mice, while L-endoglin, phosphor-Smad1/5 and platelet-endothelial cell adhesion molecule-1 levels were significantly decreased. Hyperoxia suppressed the tubular growth of human pulmonary microvascular endothelial cells (ECs), and the selective inhibition of ALK5 signalling restored tubular growth. These results indicate that hyperoxia alters the balance in two isoforms of endoglin towards increased S-endoglin and that S-endoglin attenuates TGFβ-ALK1-Smad1/5 signalling but stimulates tGfβ-ALK5-Smad2/3 signalling in pulmonary ECs, which may lead to impaired pulmonary angiogenesis in developing lungs. open Scientific RepoRtS | (2020) 10:3043 | https://doi.org/10.1038/s41598-020-59928-x www.nature.com/scientificreports www.nature.com/scientificreports/ through enhancement of the TGFβ-ALK1-Smad1/5 pathway, while connective tissue growth factor (CTGF) expression increases through enhancement of the TGFβ-ALK5-Smad2/3 pathway [27][28][29][30][31] .Several independent findings have demonstrated that endoglin is engaged in TGFβ receptor complex formation and the modulation of downstream signalling [32][33][34][35] . The expression of two alternatively spliced isoforms, long (L-) endoglin and short (S-) endoglin, has been demonstrated in human and mouse lung tissues in vivo 33,34,36,37 . L-endoglin is the predominant isoform, and its pre-mRNA can be alternatively spliced by intron retention, producing the less abundant form, S-endoglin 36,37 . Evidence indicates that L-endoglin, the predominant isoform in ECs, promotes EC proliferation via TGFβ-ALK1 signalling, whereas S-endoglin acts as an antagonist of L-endoglin via activation of the TGFβ-ALK5 pathway 32,33,36,37 .To date, most studies published on endoglin have focused on L-endoglin. It has been found that L-endoglin enhances ALK1-Smad1/5 signalling in ECs, leading to proliferation and migration, which are the main characteristics of the activation phase of angiogenesis 15,18,20,22,[38][39][40][41][42][43] . However, a role of S-endoglin during endothelial senescence was recently described 36,37 . The S-endoglin:L-endoglin ratio increases during the senescence of ECs in vitro as well ...

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“…Fibroblast is connective tissue cells that secrete type I & type III collagen (Shieh et al, 2019). Fibroblast adheres to collagen and elastic ibres which they lay down.…”

Section: Resultsmentioning

confidence: 99%

An Approach to Derive Bone Marrow Mesenchymal Stem Cells with Therapeutic Significance

Balaji

Srinivasan

Prabhu

et al. 2020

ijrps

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“Mesenchymal Stem cells (MSCs)” are distinct type of cells naturally present in the body that has the ability to separate into any cell type like bone, cartilage, muscle, nerve, tooth etc. There are numerous studies available to efficiently isolate culture, characterize and expand the bone marrow mesenchymal stem cells. Similar such method was utilized to isolate the MScs from femoral and tibial bone of female wistar rats and the standardized method was used to culture and expand MSCs. The cultured cells were determined to be MSCs with their hallmark properties of spindle shape morphometry, cellular plasticity & cell adherence property. The cells after expansion were subjected to flow cytometry analysis for characterization. The BMSCs showed positive expression for CD90 & negative expression for CD34. In the present investigation, we obtained the BMSCs that would have potential clinical significance as it was performed in a GMP environment with all necessary requirements that could enable its therapeutic value.

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TGFβ mediates collagen production in human CRSsNP nasal mucosa‐derived fibroblasts through Smad2/3‐dependent pathway and CTGF induction and secretion

Cited by 22 publications

References 33 publications

Dexamethasone Attenuates X-Ray-Induced Activation of the Autotaxin-Lysophosphatidate-Inflammatory Cycle in Breast Tissue and Subsequent Breast Fibrosis

Dexamethasone Attenuates X-Ray-Induced Activation of the Autotaxin-Lysophosphatidate-Inflammatory Cycle in Breast Tissue and Subsequent Breast Fibrosis

S-endoglin expression is induced in hyperoxia and contributes to altered pulmonary angiogenesis in bronchopulmonary dysplasia development

An Approach to Derive Bone Marrow Mesenchymal Stem Cells with Therapeutic Significance

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