ArticleAmerican journal of physiology. Lung cellular and molecular physiology2012
Osteopontin is an endogenous modulator of the constitutively activated phenotype of pulmonary adventitial fibroblasts in hypoxic pulmonary hypertension.
Article in American journal of physiology. Lung cellular and molecular physiology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers, 1 of them a synthesis that pooled it.
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Who cites it
36 citing papers in PubMed, 1 synthesis or guideline pooled it, 64 citations in OpenAlex.
- Extreme Diversity of the Human Vascular Mesenchymal Cell Landscape.Journal of the American Heart Association · 2020Pooled it
- The emerging role of integrin signaling in pulmonary vascular disease.American journal of physiology. Lung cellular and molecular physiology · 2026Review
- Single-cell and spatial profiling highlights TB-induced myofibroblasts as drivers of lung pathology.The Journal of experimental medicine · 2026Article
- Secreted Phosphoprotein 1 in Lung Diseases.Metabolites · 2025Review
- Transcriptome Analysis of Fibroblasts in Hypoxia-Induced Vascular Remodeling: Functional Roles of CD26/DPP4.International journal of molecular sciences · 2024Article
- Review
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- Clinical-radiological-pathological correlation in pulmonary hypertension with unclear and/or multifactorial mechanisms.European respiratory review : an official journal of the European Respiratory Society · 2023Article
- Identification of protein biomarkers associated with congenital diaphragmatic hernia in human amniotic fluid.Scientific reports · 2023Article
- Osteopontin in Pulmonary Hypertension.Biomedicines · 2023Review
- Clinical and Molecular Implications of Osteopontin in Heart Failure.Current issues in molecular biology · 2022Review
- Peripheral vascular remodeling during ischemia.Frontiers in pharmacology · 2022Review
- Pulmonary hypertension: Linking inflammation and pulmonary arterial stiffening.Frontiers in immunology · 2022Review
- FAM171B as a Novel Biomarker Mediates Tissue Immune Microenvironment in Pulmonary Arterial Hypertension.Mediators of inflammation · 2022Article
- An Overview of Circulating Pulmonary Arterial Hypertension Biomarkers.Frontiers in cardiovascular medicine · 2022Review
- A Novel Protective Role for Matrix Metalloproteinase-8 in the Pulmonary Vasculature.American journal of respiratory and critical care medicine · 2021Article
- Article
- Role of Osteopontin as a Potential Biomarker of Pulmonary Arterial Hypertension in Patients with Systemic Sclerosis and Other Connective Tissue Diseases (CTDs).Pharmaceuticals (Basel, Switzerland) · 2021Article
- The role of Smad2 and Smad3 in regulating homeostatic functions of fibroblasts in vitro and in adult mice.Biochimica et biophysica acta. Molecular cell research · 2020Article
- Quantification of uncertainty in a new network model of pulmonary arterial adventitial fibroblast pro-fibrotic signalling.Philosophical transactions. Series A, Mathematical, physical, and engineering sciences · 2020Article
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
Abstract
Increased cell proliferation and migration, of several cell types are key components of vascular remodeling observed in pulmonary hypertension (PH). Our previous data demonstrate that adventitial fibroblasts isolated from pulmonary arteries of chronically hypoxic hypertensive calves (termed PH-Fibs) exhibit a "constitutively activated" phenotype characterized by high proliferative and migratory potential. Osteopontin (OPN) has been shown to promote several cellular activities including growth and migration in cancer cells. We thus tested the hypothesis that elevated OPN expression confers the "activated" highly proproliferative and promigratory/invasive phenotype of PH-Fibs. Our results demonstrate that, both in vivo and ex vivo, PH-Fibs exhibited increased expression of OPN, as well as its cognate receptors, α(V)β(3) and CD44, compared with control fibroblasts (CO-Fibs). Augmented OPN expression in PH-Fibs corresponded to their high proliferative, migratory, and invasive properties and constitutive activation of ERK1/2 and AKT signaling. OPN silencing via small interfering RNA or sequestering OPN production by specific antibodies led to decreased proliferation, migration, invasion, and attenuated ERK1/2, AKT phosphorylation in PH-Fibs. Furthermore, increasing OPN levels in CO-Fibs via recombinant OPN resulted in significant increases in their proliferative, migratory, and invasive capabilities to the levels resembling those of PH-Fibs. Thus our data suggest OPN as an essential contributor to the activated (highly proliferative, migratory, and proinvasive) phenotype of pulmonary adventitial fibroblasts in hypoxic PH.
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Registered trials
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