Title |
Agonistic Anti-PDGF Receptor Autoantibodies from Patients with Systemic Sclerosis Impact Human Pulmonary Artery Smooth Muscle Cells Function In Vitro
|
---|---|
Published in |
Frontiers in immunology, February 2017
|
DOI | 10.3389/fimmu.2017.00075 |
Pubmed ID | |
Authors |
Silvia Svegliati, Donatella Amico, Tatiana Spadoni, Colomba Fischetti, Doreen Finke, Gianluca Moroncini, Chiara Paolini, Cecilia Tonnini, Antonella Grieco, Marina Rovinelli, Ada Funaro, Armando Gabrielli |
Abstract |
One of the earliest events in the pathogenesis of systemic sclerosis (SSc) is microvasculature damage with intimal hyperplasia and accumulation of cells expressing PDGF receptor. Stimulatory autoantibodies targeting PDGF receptor have been detected in SSc patients and demonstrated to induce fibrosis in vivo and convert in vitro normal fibroblasts into SSc-like cells. Since there is no evidence of the role of anti-PDGF receptor autoantibodies in the pathogenesis of SSc vascular lesions, we investigated the biologic effect of agonistic anti-PDGF receptor autoantibodies from SSc patients on human pulmonary artery smooth muscle cells and the signaling pathways involved. The synthetic (proliferation, migration, and type I collagen gene α1 chain expression) and contractile (smooth muscle-myosin heavy chain and smooth muscle-calponin expression) profiles of human pulmonary artery smooth muscle cells were assessed in vitro after incubation with SSc anti-PDGF receptors stimulatory autoantibodies. The role of reactive oxygen species, NOX isoforms, and mammalian target of rapamycin (mTOR) was investigated. Human pulmonary artery smooth muscle cells acquired a synthetic phenotype characterized by higher growth rate, migratory activity, gene expression of type I collagen α1 chain, and less expression of markers characteristic of the contractile phenotype such as smooth muscle-myosin heavy chain and smooth muscle-calponin when stimulated with PDGF and autoantibodies against PDGF receptor, but not with normal IgG. This phenotypic profile is mediated by increased generation of reactive oxygen species and expression of NOX4 and mTORC1. Our data indicate that agonistic anti-PDGF receptor autoantibodies may contribute to the pathogenesis of SSc intimal hyperplasia. |
X Demographics
As of 1 July 2024, you may notice a temporary increase in the numbers of X profiles with Unknown location. Click here to learn more.
Geographical breakdown
Country | Count | As % |
---|---|---|
United States | 1 | 20% |
France | 1 | 20% |
Unknown | 3 | 60% |
Demographic breakdown
Type | Count | As % |
---|---|---|
Members of the public | 5 | 100% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
Unknown | 28 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Student > Ph. D. Student | 9 | 32% |
Researcher | 5 | 18% |
Other | 3 | 11% |
Student > Bachelor | 1 | 4% |
Unspecified | 1 | 4% |
Other | 2 | 7% |
Unknown | 7 | 25% |
Readers by discipline | Count | As % |
---|---|---|
Medicine and Dentistry | 10 | 36% |
Biochemistry, Genetics and Molecular Biology | 4 | 14% |
Immunology and Microbiology | 2 | 7% |
Nursing and Health Professions | 1 | 4% |
Unspecified | 1 | 4% |
Other | 2 | 7% |
Unknown | 8 | 29% |