scholarly journals Pathologic Proteolytic Processing of N-Cadherin as a Marker of Human Fibrotic Disease

Cells ◽  
2022 ◽  
Vol 11 (1) ◽  
pp. 156
Author(s):  
Paul Durham Ferrell ◽  
Kristianne Michelle Oristian ◽  
Everett Cockrell ◽  
Salvatore Vincent Pizzo
Keyword(s):  
Idiopathic Pulmonary Fibrosis ◽  
Pulmonary Fibrosis ◽  
Cell Surface ◽  
Cell Lines ◽  
Cell Adhesion Molecule ◽  
Protein Processing ◽  
Proteolytic Processing ◽  
Fibrotic Disease ◽  
Nonalcoholic Fatty Liver ◽  
Murine Antibody

Prior research has implicated the involvement of cell adhesion molecule N-cadherin in tissue fibrosis and remodeling. We hypothesize that anomalies in N-cadherin protein processing are involved in pathological fibrosis. Diseased tissues associated with fibrosis of the heart, lung, and liver were probed for the precursor form of N-cadherin, pro-N-cadherin (PNC), by immunohistochemistry and compared to healthy tissues. Myofibroblast cell lines were analyzed for cell surface pro-N-cadherin by flow cytometry and immunofluorescent microscopy. Soluble PNC products were immunoprecipitated from patient plasmas and an enzyme-linked immunoassay was developed for quantification. All fibrotic tissues examined show aberrant PNC localization. Cell surface PNC is expressed in myofibroblast cell lines isolated from cardiomyopathy and idiopathic pulmonary fibrosis but not on myofibroblasts isolated from healthy tissues. PNC is elevated in the plasma of patients with cardiomyopathy (p ≤ 0.0001), idiopathic pulmonary fibrosis (p ≤ 0.05), and nonalcoholic fatty liver disease with cirrhosis (p ≤ 0.05). Finally, we have humanized a murine antibody and demonstrate that it significantly inhibits migration of PNC expressing myofibroblasts. Collectively, the aberrant localization of PNC is observed in all fibrotic tissues examined in our study and our data suggest a role for cell surface PNC in the pathogenesis of fibrosis.

Tu1853 Idiopathic Pulmonary Fibrosis Is Associated With Increased Impedance Measures of Reflux Compared to Non-Fibrotic Disease Among Pre-Lung Transplant Patients

2014 ◽  
Vol 146 (5) ◽  
pp. S-855-S-856
Author(s):  
Sravanya Gavini ◽  
Raymond T. Finn ◽  
Wai-Kit Lo ◽  
Hilary J. Goldberg ◽  
Robert Burakoff ◽  
...  
Keyword(s):  
Idiopathic Pulmonary Fibrosis ◽  
Pulmonary Fibrosis ◽  
Lung Transplant ◽  
Fibrotic Disease ◽  
Transplant Patients

Proteomics in idiopathic pulmonary fibrosis: the quest for biomarkers

2021 ◽  
Author(s):  
Tila Khan ◽  
Sanjukta Dasgupta ◽  
Nilanjana Ghosh ◽  
Koel Chaudhury
Keyword(s):  
Animal Models ◽  
Idiopathic Pulmonary Fibrosis ◽  
Pulmonary Fibrosis ◽  
Cell Lines ◽  
Proteomics Analysis

This review focuses on proteomics analysis of biofluids derived from IPF patients, animal models of pulmonary fibrosis and cell lines.

scholarly journals Greater cellular stiffness in fibroblasts from patients with idiopathic pulmonary fibrosis

2018 ◽  
Vol 315 (1) ◽  
pp. L59-L65 ◽  
Author(s):  
Jade Jaffar ◽  
Soung-Hee Yang ◽  
Sally Yunsun Kim ◽  
Hae-Won Kim ◽  
Alen Faiz ◽  
...  
Keyword(s):  
Idiopathic Pulmonary Fibrosis ◽  
Pulmonary Fibrosis ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β1 ◽  
Cellular Level ◽  
Lung Fibroblasts ◽  
Fibrotic Disease ◽  
Force Microscopy ◽  
Atomic Force ◽  
Organ Tissue

Idiopathic pulmonary fibrosis (IPF) is a lethal lung disease involving degenerative breathing capacity. Fibrotic disease is driven by dysregulation in mechanical forces at the organ, tissue, and cellular level. While it is known that, in certain pathologies, diseased cells are stiffer than healthy cells, it is not known if fibroblasts derived from patients with IPF are stiffer than their normal counterparts. Using IPF patient-derived cell cultures, we measured the stiffness of individual lung fibroblasts via high-resolution force maps using atomic force microscopy. Fibroblasts from patients with IPF were stiffer and had an augmented cytoskeletal response to transforming growth factor-β1 compared with fibroblasts from donors without IPF. The results from this novel study indicate that the increased stiffness of lung fibroblasts of IPF patients may contribute to the increased rigidity of fibrotic lung tissue.

scholarly journals Idiopathic Pulmonary Fibrosis: Best Practice in Monitoring and Managing a Relentless Fibrotic Disease

Respiration ◽  
2019 ◽  
Vol 99 (1) ◽  
pp. 73-82 ◽  
Author(s):  
Wim A. Wuyts ◽  
Marlies Wijsenbeek ◽  
Benjamin Bondue ◽  
Demosthenes Bouros ◽  
Paul Bresser ◽  
...  
Keyword(s):  
Idiopathic Pulmonary Fibrosis ◽  
Pulmonary Fibrosis ◽  
Best Practice ◽  
Fibrotic Disease

scholarly journals Proteomic Analysis Reveals Key Proteins in Extracellular Vesicles Cargo Associated with Idiopathic Pulmonary Fibrosis In Vitro

Biomedicines ◽  
2021 ◽  
Vol 9 (8) ◽  
pp. 1058
Author(s):  
Juan Manuel Velázquez-Enríquez ◽  
Jovito Cesar Santos-Álvarez ◽  
Alma Aurora Ramírez-Hernández ◽  
Edilburga Reyes-Jiménez ◽  
Armando López-Martínez ◽  
...  
Keyword(s):  
Idiopathic Pulmonary Fibrosis ◽  
Pulmonary Fibrosis ◽  
Cell Lines ◽  
Extracellular Vesicles ◽  
Proteomic Analysis ◽  
Fibroblast Cell ◽  
Differentially Expressed ◽  
Differentially Expressed Proteins ◽  
Collagen Chain ◽  
Fibroblast Cell Lines

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, irreversible, and highly fatal disease. It is characterized by the increased activation of both fibroblast and myofibroblast that results in excessive extracellular matrix (ECM) deposition. Extracellular vesicles (EVs) have been described as key mediators of intercellular communication in various pathologies. However, the role of EVs in the development of IPF remains poorly understood. This study aimed to characterize the differentially expressed proteins contained within EVs cargo derived from the fibroblast cell lines LL97A (IPF-1) and LL29 (IPF-2) isolated from lungs bearing IPF as compared to those derived from the fibroblast cell lines CCD8Lu (NL-1) and CCD19Lu (NL-2) isolated from healthy donors. Isolated EVs were subjected to label-free quantitative proteomic analysis by LC-MS/MS, and as a result, 331 proteins were identified. Differentially expressed proteins were obtained after the pairwise comparison, including all experimental groups. A total of 86 differentially expressed proteins were identified in either one or more comparison groups. Of note, proteins involved in fibrogenic processes, such as tenascin-c (TNC), insulin-like-growth-factor-binding protein 7 (IGFBP7), fibrillin-1 (FBN1), alpha-2 collagen chain (I) (COL1A2), alpha-1 collagen chain (I) (COL1A1), and lysyl oxidase homolog 1 (LOXL1), were identified in EVs cargo isolated from IPF cell lines. Additionally, KEGG pathway enrichment analysis revealed that differentially expressed proteins participate in focal adhesion, PI3K-Akt, and ECM–receptor interaction signaling pathways. In conclusion, our findings reveal that proteins contained within EVs cargo might play key roles during IPF pathogenesis.

scholarly journals The changing treatment landscape in idiopathic pulmonary fibrosis

2015 ◽  
Vol 24 (135) ◽  
pp. 65-68 ◽  
Author(s):  
Ulrich Costabel
Keyword(s):  
Idiopathic Pulmonary Fibrosis ◽  
Pulmonary Fibrosis ◽  
Median Survival ◽  
Fibrotic Disease ◽  
Long Time ◽  
Key Events ◽  
Made In

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive and irreversible fibrotic disease of the lung that has greatly frustrated clinicians for a long time. The prognosis of IPF (median survival 2–5 years following diagnosis) is poorer than that of some cancers and for many years no significant advances were made in its management. However, between 2011 and 2014 a number of pivotal developments were made that have improved the outlook for patients with IPF. Herein, we review this rapidly changing landscape, discussing key events whilst still acknowledging that IPF remains a challenging disease to diagnose and manage.

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