Hepatocyte Growth Factor Attenuates the Development of TGF-β1- Induced EndMT through Down-regulating the Notch Signaling

Idiopathic pulmonary fibrosis (IPF), the most common form of idiopathic interstitial pneumonia, is a progressive, irreversible, and typically lethal disease characterized by an abnormal fibrotic response involving vast areas of the lungs. Given the poor knowledge of the mechanisms underpinning IPF onset and progression, a better understanding of the cellular processes and molecular pathways involved is essential for the development of effective therapies, currently lacking. Besides a number of established IPF-associated risk factors, such as cigarette smoking, environmental factors, comorbidities, and viral infections, several other processes have been linked with this devastating disease. Apoptosis, senescence, epithelial-mesenchymal transition, endothelial-mesenchymal transition, and epithelial cell migration have been shown to play a key role in IPF-associated tissue remodeling. Moreover, molecules, such as chemokines, cytokines, growth factors, adenosine, glycosaminoglycans, non-coding RNAs, and cellular processes including oxidative stress, mitochondrial dysfunction, endoplasmic reticulum stress, hypoxia, and alternative polyadenylation have been linked with IPF development. Importantly, strategies targeting these processes have been investigated to modulate abnormal cellular phenotypes and maintain tissue homeostasis in the lung. This review provides an update regarding the emerging cellular and molecular mechanisms involved in the onset and progression of IPF.

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“…Moreover, TGF-β signaling exerts its effects by interacting with other signaling cascades, including Wnt and Notch (Fig. 5a, c) [267][268][269].…”

Section: Endothelial-mesenchymal Transition (Endmt)mentioning

confidence: 99%

Emerging cellular and molecular determinants of idiopathic pulmonary fibrosis

Phan

Paliogiannis

Nasrallah

et al. 2020

Cell. Mol. Life Sci.

214

152

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“…In addition, even if not directly investigated in SSc, hepatocyte growth factor and the aldosterone receptor-blocker spironolactone were found to prevent TGF-β1-induced EndoMT in human umbilical vein ECs [ 119 , 149 , 150 ]. Finally, TGF-β1-induced EndoMT was reverted after treatment with triazole arginylglycylaspartic acid antagonist in endothelial precursor cells [ 151 ].…”

Section: Main Molecular Pathways Driving Myofibroblast Differentiation From Vascular Wall Residing Cells In Systemic Sclerosis and Relatementioning

confidence: 99%

New Insights into Profibrotic Myofibroblast Formation in Systemic Sclerosis: When the Vascular Wall Becomes the Enemy

Romano

Rosa

Fioretto

et al. 2021

Life

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In systemic sclerosis (SSc), abnormalities in microvessel morphology occur early and evolve into a distinctive vasculopathy that relentlessly advances in parallel with the development of tissue fibrosis orchestrated by myofibroblasts in nearly all affected organs. Our knowledge of the cellular and molecular mechanisms underlying such a unique relationship between SSc-related vasculopathy and fibrosis has profoundly changed over the last few years. Indeed, increasing evidence has suggested that endothelial-to-mesenchymal transition (EndoMT), a process in which profibrotic myofibroblasts originate from endothelial cells, may take center stage in SSc pathogenesis. While in arterioles and small arteries EndoMT may lead to the accumulation of myofibroblasts within the vessel wall and development of fibroproliferative vascular lesions, in capillary vessels it may instead result in vascular destruction and formation of myofibroblasts that migrate into the perivascular space with consequent tissue fibrosis and microvessel rarefaction, which are hallmarks of SSc. Besides endothelial cells, other vascular wall-resident cells, such as pericytes and vascular smooth muscle cells, may acquire a myofibroblast-like synthetic phenotype contributing to both SSc-related vascular dysfunction and fibrosis. A deeper understanding of the mechanisms underlying the differentiation of myofibroblasts inside the vessel wall provides the rationale for novel targeted therapeutic strategies for the treatment of SSc.

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“…Increasing evidence demonstrates that EndMT is vital for production of myofibroblasts in fibrotic tissues or organs ( Zeisberg et al, 2007 ; Potenta et al, 2008 ; Zeisberg et al, 2008 ; Li et al, 2009 ). It has been reported that TGF-β can act as an upstream modulator in stimulation of EndMT ( Hou et al, 2019 ; Yang et al, 2019b ). The enhanced expression of TGF-β1 induces an increase in inflammatory factors and asymmetric dimethylarginine (ADMA), whereas a decrease occurs in Nrf2, dimethyl arginine dimethylaminohydrolase-1 (DDAH1), VE-cadherin, secretion of nitric oxide (NO) and activity of nitric oxide synthase (NOS).…”

Section: Curcumin and Transforming Growth Factor-beta In Different DImentioning

confidence: 99%

Toward Regulatory Effects of Curcumin on Transforming Growth Factor-Beta Across Different Diseases: A Review

et al. 2020

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Immune response, proliferation, migration and angiogenesis are juts a few of cellular events that are regulated by transforming growth factor-β (TGF-β) in cells. A number of studies have documented that TGF-β undergoes abnormal expression in different diseases, e.g., diabetes, cancer, fibrosis, asthma, arthritis, among others. This has led to great fascination into this signaling pathway and developing agents with modulatory impact on TGF-β. Curcumin, a natural-based compound, is obtained from rhizome and roots of turmeric plant. It has a number of pharmacological activities including antioxidant, anti-inflammatory, anti-tumor, anti-diabetes and so on. Noteworthy, it has been demonstrated that curcumin affects different molecular signaling pathways such as Wnt/β-catenin, Nrf2, AMPK, mitogen-activated protein kinase and so on. In the present review, we evaluate the potential of curcumin in regulation of TGF-β signaling pathway to corelate it with therapeutic impacts of curcumin. By modulation of TGF-β (both upregulation and down-regulation), curcumin ameliorates fibrosis, neurological disorders, liver disease, diabetes and asthma. Besides, curcumin targets TGF-β signaling pathway which is capable of suppressing proliferation of tumor cells and invading cancer cells.

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Hepatocyte Growth Factor Attenuates the Development of TGF-β1- Induced EndMT through Down-regulating the Notch Signaling

Cited by 7 publications

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Emerging cellular and molecular determinants of idiopathic pulmonary fibrosis

Emerging cellular and molecular determinants of idiopathic pulmonary fibrosis

New Insights into Profibrotic Myofibroblast Formation in Systemic Sclerosis: When the Vascular Wall Becomes the Enemy

Toward Regulatory Effects of Curcumin on Transforming Growth Factor-Beta Across Different Diseases: A Review

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