Faculty Opinions recommendation of HLA class I molecules partner with integrin β4 to stimulate endothelial cell proliferation and migration.
Year: 2011
Type: peer-review
Abstract: Among transplant recipients, those who produce antibodies against the donor's human leukocyte antigens (HLAs) are at higher risk for antibody-mediated rejection and transplant vasculopathy, which is a progressive, vasculo-occlusive disease that results in ischemic injury and deterioration of organ function.Antibodies against HLA class I (HLA-I) molecules are thought to contribute to transplant vasculopathy by triggering signals that elicit the activation and proliferation of endothelial cells.Here, we demonstrate a molecular association between HLA-I and the integrin β 4 subunit after the stimulation of endothelial cells with HLA-I-specific antibodies.Knockdown of integrin β 4 in these cells abrogated the ability of HLA-I to stimulate the phosphorylation of the kinases Akt, extracellular signal-regulated kinase (ERK), and Src, as well as cellular proliferation.Similarly, reducing the abundance of HLA-I suppressed integrin β 4 -mediated phosphorylation of ERK and the migration of endothelial cells on laminin-5, a component of the extracellular matrix.These results indicate a mutual dependency between HLA-I and the integrin β 4 subunit to stimulate the proliferation and migration of endothelial cells, which may be important in promoting transplant vasculopathy and tumor angiogenesis.
Author: Joyce Solheim
Institution: University of Nebraska Medical Center
Language: English
Subfield: Immunology and Allergy
Field: Medicine
Domain: Health Sciences
Open Access status: green
Awards: Targeting crosstalk between insulin and Gq signaling systems in pancreatic cancer, Development of Transplant Strategies Uniquely Responsive to the Needs of Children, G490132536, GI PEPTIDE SIGNALING THROUGH TYROSINE PHOSPHORYLATION, CURE: Digestive Diseases Research Center, Gastrointestinal Peptide Signaling through PKC/PKD, G9000103220
OpenAlex ID: W4206649749