scholarly journals Integrating mechanisms of pulmonary fibrosis

2011 ◽  
Vol 208 (7) ◽  
pp. 1339-1350 ◽  
Author(s):  
Thomas A. Wynn
Keyword(s):  
Pulmonary Fibrosis ◽  
Molecular Mechanisms ◽  
Complex Disease ◽  
Pathological Process ◽  
Therapeutic Options ◽  
Pathogenic Mechanisms ◽  
The Way

Pulmonary fibrosis is a highly heterogeneous and lethal pathological process with limited therapeutic options. Although research on the pathogenesis of pulmonary fibrosis has frequently focused on the mechanisms that regulate the proliferation, activation, and differentiation of collagen-secreting myofibroblasts, recent studies have identified new pathogenic mechanisms that are critically involved in the initiation and progression of fibrosis in a variety of settings. A more detailed and integrated understanding of the cellular and molecular mechanisms of pulmonary fibrosis could help pave the way for effective therapeutics for this devastating and complex disease.

scholarly journals Cellular Senescence: Pathogenic Mechanisms in Lung Fibrosis

2021 ◽  
Author(s):  
Tanyalak Parimon ◽  
Miriam Hohmann ◽  
Changfu Yao
Keyword(s):  
Pulmonary Fibrosis ◽  
Cellular Senescence ◽  
Lung Fibrosis ◽  
Molecular Mechanisms ◽  
Current Knowledge ◽  
Alveolar Type ◽  
Basal Cells ◽  
Regulatory Pathways ◽  
Pathogenic Mechanisms

:Pulmonary fibrosis is a chronic and fatal lung disease that significantly impacts the aging population globally. To date, anti-fibrotic, immunosuppressive, and other adjunct therapy demonstrate a limited efficacy. Advancing our understanding of pathogenic mechanisms of lung fibrosis provides a future path for the cure. Cellular senescence has gained substantial interest in the past decades due to the increased incidence of fibroproliferative lung diseases in the older age group. Furthermore, the pathologic state of cellular senescence that includes maladaptive tissue repair, decreased regeneration, and chronic inflammation resembles key features of progressive lung fibrosis. This review describes regulatory pathways of cellular senescence and discusses the current knowledge on the senescence of critical cellular players of lung fibrosis, including epithelial cells (alveolar type 2 cells, basal cells, etc.), fibroblasts, and immune cells, their phenotypic changes, and the cellular and molecular mechanisms by which these cells contribute to the pathogenesis of pulmonary fibrosis. A few challenges in the field include establishing appropriate in vivo experimental models and identifying senescence targeted signaling molecules and specific therapy to target senescent cells, known collectively as "senolytic" or “senotherapeutic” agents.

scholarly journals Cellular Senescence: Pathogenic Mechanisms in Lung Fibrosis

2021 ◽  
Vol 22 (12) ◽  
pp. 6214
Author(s):  
Tanyalak Parimon ◽  
Miriam S. Hohmann ◽  
Changfu Yao
Keyword(s):  
Pulmonary Fibrosis ◽  
Cellular Senescence ◽  
Lung Fibrosis ◽  
Molecular Mechanisms ◽  
Current Knowledge ◽  
Alveolar Type ◽  
Basal Cells ◽  
Regulatory Pathways ◽  
Pathogenic Mechanisms

Pulmonary fibrosis is a chronic and fatal lung disease that significantly impacts the aging population globally. To date, anti-fibrotic, immunosuppressive, and other adjunct therapy demonstrate limited efficacies. Advancing our understanding of the pathogenic mechanisms of lung fibrosis will provide a future path for the cure. Cellular senescence has gained substantial interest in recent decades due to the increased incidence of fibroproliferative lung diseases in the older age group. Furthermore, the pathologic state of cellular senescence that includes maladaptive tissue repair, decreased regeneration, and chronic inflammation resembles key features of progressive lung fibrosis. This review describes regulatory pathways of cellular senescence and discusses the current knowledge on the senescence of critical cellular players of lung fibrosis, including epithelial cells (alveolar type 2 cells, basal cells, etc.), fibroblasts, and immune cells, their phenotypic changes, and the cellular and molecular mechanisms by which these cells contribute to the pathogenesis of pulmonary fibrosis. A few challenges in the field include establishing appropriate in vivo experimental models and identifying senescence-targeted signaling molecules and specific therapies to target senescent cells, known collectively as “senolytic” or “senotherapeutic” agents.

scholarly journals Anti-Fibrosis Effects of Magnesium Lithospermate B in Experimental Pulmonary Fibrosis: By Inhibiting TGF-βRI/Smad Signaling

Molecules ◽  
2021 ◽  
Vol 26 (6) ◽  
pp. 1715
Author(s):  
Xin Luo ◽  
Qiangqiang Deng ◽  
Yaru Xue ◽  
Tianwei Zhang ◽  
Zhitao Wu ◽  
...  
Keyword(s):  
Pulmonary Fibrosis ◽  
Cell Line ◽  
Molecular Mechanisms ◽  
Transforming Growth Factor ◽  
Salvia Miltiorrhiza ◽  
A549 Cells ◽  
Epithelial Cell Line ◽  
Human Lung Fibroblast ◽  
Magnesium Lithospermate B

Pulmonary fibrosis is a severe and irreversible interstitial pulmonary disease with high mortality and few treatments. Magnesium lithospermate B (MLB) is a hydrosoluble component of Salvia miltiorrhiza and has been reported to have antifibrotic effects in other forms of tissue fibrosis. In this research, we studied the effects of MLB on pulmonary fibrosis and the underlying mechanisms. Our results indicated that MLB treatment (50 mg/kg) for seven days could attenuate bleomycin (BLM)-induced pulmonary fibrosis by reducing the alveolar structure disruption and collagen deposition in the C57 mouse model. MLB was also found to inhibit transforming growth factor-beta (TGF-β)-stimulated myofibroblastic transdifferentiation of human lung fibroblast cell line (MRC-5) cells and collagen production by human type II alveolar epithelial cell line (A549) cells, mainly by decreasing the expression of TGF-β receptor I (TGF-βRI) and regulating the TGF-β/Smad pathway. Further studies confirmed that the molecular mechanisms of MLB in BLM-induced pulmonary fibrosis mice were similar to those observed in vitro. In summary, our results demonstrated that MLB could alleviate experimental pulmonary fibrosis both in vivo and in vitro, suggesting that MLB has great potential for pulmonary fibrosis treatment.

scholarly journals LRG1 Promotes Metastatic Dissemination of Melanoma through Regulating EGFR/STAT3 Signalling

Cancers ◽  
2021 ◽  
Vol 13 (13) ◽  
pp. 3279
Author(s):  
Yuet Ping Kwan ◽  
Melissa Hui Yen Teo ◽  
Jonathan Chee Woei Lim ◽  
Michelle Siying Tan ◽  
Graciella Rosellinny ◽  
...  
Keyword(s):  
Metastatic Melanoma ◽  
Melanoma Cell ◽  
Molecular Mechanisms ◽  
Complex Disease ◽  
Treatment Options ◽  
Melanoma Metastasis ◽  
Dependent Manner ◽  
Promoting Effect ◽  
Human Patient ◽  
Cell Invasiveness

Although less common, melanoma is the deadliest form of skin cancer largely due to its highly metastatic nature. Currently, there are limited treatment options for metastatic melanoma and many of them could cause serious side effects. A better understanding of the molecular mechanisms underlying the complex disease pathophysiology of metastatic melanoma may lead to the identification of novel therapeutic targets and facilitate the development of targeted therapeutics. In this study, we investigated the role of leucine-rich α-2-glycoprotein 1 (LRG1) in melanoma development and progression. We first established the association between LRG1 and melanoma in both human patient biopsies and mouse melanoma cell lines and revealed a significant induction of LRG1 expression in metastatic melanoma cells. We then showed no change in tumour cell growth, proliferation, and angiogenesis in the absence of the host Lrg1. On the other hand, there was reduced melanoma cell metastasis to the lungs in Lrg1-deficient mice. This observation was supported by the promoting effect of LRG1 in melanoma cell migration, invasion, and adhesion. Mechanistically, LRG1 mediates melanoma cell invasiveness in an EGFR/STAT3-dependent manner. Taken together, our studies provided compelling evidence that LRG1 is required for melanoma metastasis but not growth. Targeting LRG1 may offer an alternative strategy to control malignant melanoma.

When things go wrong: Exploring possible mechanisms driving the progressive fibrosis phenotype in interstitial lung diseases

2021 ◽  
pp. 2004507
Author(s):  
Moisés Selman ◽  
Annie Pardo
Keyword(s):  
Pulmonary Fibrosis ◽  
Lung Diseases ◽  
Molecular Mechanisms ◽  
Lung Parenchyma ◽  
Interstitial Lung Diseases ◽  
Unknown Etiology ◽  
Clinical Behavior ◽  
The Past ◽  
Appropriate Treatment ◽  
Different Types

Interstitial lung diseases (ILD) comprise a large and heterogeneous group of disorders of known and unknown etiology characterised by diffuse damage of the lung parenchyma. In the past years, it has become evident that patients with different types of ILD are at risk of developing progressive pulmonary fibrosis known as pulmonary fibrosing ILD (PF-ILD). This is a phenotype behaving similar to idiopathic pulmonary fibrosis, the archetypical example of progressive fibrosis. PF-ILD is not a distinct clinical entity but describes a group of ILD with a similar clinical behavior. This phenotype may occur in diseases displaying distinct etiologies and different biopathology during their initiation and development. Importantly, these entities may have the potential for improvement or stabilisation prior to entering in the progressive fibrosing phase. The crucial questions are (1) why a subset of patients develops a progressive and irreversible fibrotic phenotype even with appropriate treatment, and (2) what the pathogenic mechanisms driving progression possibly are. We here provide a framework highlighting putative mechanisms underlying progression, including genetic susceptibility, aging, epigenetics, the structural fibrotic distortion, the aberrant composition and stiffness of the extracellular matrix, and the emergence of distinct profibrotic cell subsets. Understanding the cellular and molecular mechanisms behind PF-ILD will provide the basis for identifying risk factors and appropriate therapeutical strategies.

scholarly journals Anti-fibrosis effect for Hirsutella sinensis mycelium based on inhibition of mTOR p70S6K phosphorylation

2017 ◽  
Vol 23 (7) ◽  
pp. 615-624 ◽  
Author(s):  
Huimin Yue ◽  
Yarong Zhao ◽  
Haining Wang ◽  
Feiya Ma ◽  
Fei Liu ◽  
...  
Keyword(s):  
Pulmonary Fibrosis ◽  
Lung Fibrosis ◽  
Molecular Mechanisms ◽  
Histopathological Examination ◽  
Smooth Muscle Actin ◽  
A549 Cells ◽  
Mtor Pathway ◽  
Cordyceps Sinensis ◽  
Tgf Β1

Hirsutella sinensis, cultured in vitro, is an attractive substitute for Cordyceps sinensis as health supplement. The aim of this study was to demonstrate whether H. sinensis mycelium (HSM) attenuates murine pulmonary fibrosis induced by bleomycin and to explore the underlying molecular mechanisms. Using lung fibrosis modle induced by intratracheal instillation of bleomycin (BLM; 4 mg/kg), we observed that the administration of HSM reduced HYP, TGF-β1 and the production of several pro-fibrosis cytokines (α-smooth muscle actin, fibronectin and vimentin) in fibrotic mice lung sections. Histopathological examination of lung tissues also demonstrated that HSM improved BLM-induced pathological damage. Concurrently, HSM supplementation markedly reduced the chemotaxis of alveolar macrophages and potently suppressed the expression of inflammatory cytokines. Also, HSM influenced Th1/Th2 and Th17/Treg imbalance and blocked the phosphorylation of mTOR pathway in vivo. Alveolar epithelial A549 cells acquired a mesenchymal phenotype and an increased expression of myofibroblast markers of differentiation (vimentin and fibronectin) after treatment with TGF-β1. HSM suppressed these markers and blocked the phosphorylation of mTOR pathway in vitro. The results provide evidence supporting the use of HSM in the intervention of pulmonary fibrosis and suggest that HSM is a potential therapeutic agent for lung fibrosis.

Molecular mechanisms of pulmonary fibrosis

10.2741/a877 ◽  
2002 ◽  
Vol 7 (4) ◽  
pp. d1743-1761 ◽  
Author(s):  
Moises Selman
Keyword(s):  
Pulmonary Fibrosis ◽  
Molecular Mechanisms

scholarly journals The disorder of the iron metabolism as a possible mechanism for the development of neurodegeneration after new coronavirus infection of SARS-CoV-2

2021 ◽  
Vol 40 (4) ◽  
pp. 13-24
Author(s):  
Igor V. Litvinenko ◽  
Igor V. Krasakov
Keyword(s):  
Nervous System ◽  
Neurodegenerative Diseases ◽  
Iron Metabolism ◽  
Iron Homeostasis ◽  
Molecular Mechanisms ◽  
Brain Structures ◽  
Pathological Process ◽  
Parkinsons Disease ◽  
Neurodegenerative Process ◽  
Coronavirus Infection

The involvement of the nervous system in the pathological process that occurs when COVID-19 is infected is becoming more and more obvious. The question of the possibility of the debut or progression of the already developed Parkinsonism syndrome in patients who have undergone COVID-19 is regularly raised. A large number of hypotheses are put forward to explain this relationship. It is assumed that a violation of iron metabolism in the brain may underlie the development and progression of neurodegenerative diseases, including after the new coronavirus infection SARS-CoV-2. The analysis of stu dies on the possible influence of iron metabolism disorders on the occurrence and mechanism of development of neurodegenerative diseases after infection with SARS-CoV-2 has been carried out. The processes of physiological maintenance of iron homeostasis, as well as the influence of physiological aging on the accumulation of iron in the central nervous system are described. The relationship between hyperferritinemia occurring in COVID-19 and ferroptosis as the basis of the neurodegenerative process in Parkinsons disease and Alzheimers disease is discussed. The main molecular mechanisms involved in ferroptosis are described. Examples of involvement of metal homeostasis disorders in the process of altering the structure of -synuclein, synthesis of -amyloid, hyperphosphorylated tau- protein are given. The causes of excessive iron accumulation in certain brain structures are discussed. The question of the possibility of using the assessment of changes in iron metabolism as a new biomarker of the progression of Parkinsons disease is analyzed. (1 figure, bibliography: 62 refs)

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