Differential expression of the FAK family kinases in rheumatoid arthritis and osteoarthritis synovial tissues |
| |
Authors: | Shiva Shahrara Hernan P Castro-Rueda G Kenneth Haines Alisa E Koch |
| |
Institution: | (1) Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611, USA;(2) Department of Pathology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611, USA;(3) Department of Pathology, Yale University School of Medicine, New Haven, Connecticut 06511, USA;(4) Veteran's Administration,Chicago Health Care System, Lakeside Division, Chicago Health Care System, Chicago, Illinois 60611, USA;(5) Veteran's Administration and the University of Michigan Medical Center, Ann Arbor, Michigan 48109, USA |
| |
Abstract: | The focal adhesion kinase (FAK) family kinases, including FAK and proline-rich kinase 2 (Pyk)2, are the predominant mediators
of integrin αvβ3 signaling events that play an important role in cell adhesion, osteoclast pathology, and angiogenesis, all
processes important in rheumatoid arthritis (RA). Using immunohistochemical and western blot analysis, we studied the distribution
of phospho (p)FAK, pPyk2, pSrc, pPaxillin and pPLCγ in the synovial tissue (ST) from patients with RA, osteoarthritis (OA)
and normal donors (NDs) as well as in RA ST fibroblasts and peripheral blood differentiated macrophages (PB MΦs) treated with
tumor necrosis factor-α (TNFα) or interleukin-1β (IL1β). RA and OA STs showed a greater percentage of pFAK on lining cells
and MΦs compared with ND ST. RA ST fibroblasts expressed pFAK at baseline, which increased with TNFα or IL1β stimulation.
Pyk2 and Src were phosphorylated more on RA versus OA and ND lining cells and MΦs. pPyk2 was expressed on RA ST fibrobasts
but not in MΦs at baseline, however it was upregulated upon TNFα or IL1β activation in both cell types. pSrc was expressed
in RA ST fibroblasts and MΦs at baseline and was further increased by TNFα or IL1β stimulation. pPaxillin and pPLCγ were upregulated
in RA versus OA and ND lining cells and sublining MΦs. Activation of the FAK family signaling cascade on RA and OA lining
cells may be responsible for cell adhesion and migration into the diseased STs. Therapies targeting this novel signaling pathway
may be beneficial in RA. |
| |
Keywords: | |
本文献已被 PubMed SpringerLink 等数据库收录! |
|