Cargando…

Differential expression of the FAK family kinases in rheumatoid arthritis and osteoarthritis synovial tissues

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)....

Descripción completa

Detalles Bibliográficos
Autores principales: Shahrara, Shiva, Castro-Rueda, Hernan P, Haines, G Kenneth, Koch, Alisa E
Formato: Texto
Lenguaje:English
Publicado: BioMed Central 2007
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2212559/
https://www.ncbi.nlm.nih.gov/pubmed/17963503
http://dx.doi.org/10.1186/ar2318
_version_ 1782148723332087808
author Shahrara, Shiva
Castro-Rueda, Hernan P
Haines, G Kenneth
Koch, Alisa E
author_facet Shahrara, Shiva
Castro-Rueda, Hernan P
Haines, G Kenneth
Koch, Alisa E
author_sort Shahrara, Shiva
collection PubMed
description 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.
format Text
id pubmed-2212559
institution National Center for Biotechnology Information
language English
publishDate 2007
publisher BioMed Central
record_format MEDLINE/PubMed
spelling pubmed-22125592008-01-24 Differential expression of the FAK family kinases in rheumatoid arthritis and osteoarthritis synovial tissues Shahrara, Shiva Castro-Rueda, Hernan P Haines, G Kenneth Koch, Alisa E Arthritis Res Ther Research Article 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. BioMed Central 2007 2007-10-26 /pmc/articles/PMC2212559/ /pubmed/17963503 http://dx.doi.org/10.1186/ar2318 Text en Copyright © 2007 Koch et al.; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an open access article distributed under the terms of the Creative Commons Attribution License ( (http://creativecommons.org/licenses/by/2.0) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Shahrara, Shiva
Castro-Rueda, Hernan P
Haines, G Kenneth
Koch, Alisa E
Differential expression of the FAK family kinases in rheumatoid arthritis and osteoarthritis synovial tissues
title Differential expression of the FAK family kinases in rheumatoid arthritis and osteoarthritis synovial tissues
title_full Differential expression of the FAK family kinases in rheumatoid arthritis and osteoarthritis synovial tissues
title_fullStr Differential expression of the FAK family kinases in rheumatoid arthritis and osteoarthritis synovial tissues
title_full_unstemmed Differential expression of the FAK family kinases in rheumatoid arthritis and osteoarthritis synovial tissues
title_short Differential expression of the FAK family kinases in rheumatoid arthritis and osteoarthritis synovial tissues
title_sort differential expression of the fak family kinases in rheumatoid arthritis and osteoarthritis synovial tissues
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2212559/
https://www.ncbi.nlm.nih.gov/pubmed/17963503
http://dx.doi.org/10.1186/ar2318
work_keys_str_mv AT shahrarashiva differentialexpressionofthefakfamilykinasesinrheumatoidarthritisandosteoarthritissynovialtissues
AT castroruedahernanp differentialexpressionofthefakfamilykinasesinrheumatoidarthritisandosteoarthritissynovialtissues
AT hainesgkenneth differentialexpressionofthefakfamilykinasesinrheumatoidarthritisandosteoarthritissynovialtissues
AT kochalisae differentialexpressionofthefakfamilykinasesinrheumatoidarthritisandosteoarthritissynovialtissues