Expression and Functional Significance of Alternatively Spliced CS1 Fibronectin in Rheumatoid Arthritis Microvasculature

Overview

Journal J Clin Invest

Specialty General Medicine

Date 1994 Jan 1

PMID 8282813

Citations 45

Authors

M J Elices

V Tsai

D Strahl

A S Goel

V Tollefson

T Arrhenius

E A Wayner

F C Gaeta

J D Fikes

G S Firestein

Affiliations

Soon will be listed here.

Abstract

Expression of fibronectin (FN) isoforms containing CS1, a 25-amino acid sequence present within the alternatively spliced IIICS region of FN, has been analyzed in rheumatoid arthritis (RA) synovium. Unexpectedly, CS1-containing FN variants were exclusively found on endothelium but not extracellular matrix (ECM) of RA synovium. Lumenal expression of CS1 on RA endothelial cells, as observed by electron microscopy, correlated with inflammation in RA, since normal synovium expressed little CS1 without appreciable decrease in ECM FN. CS1 expression on human endothelial cells was further shown by FN mRNA analyses. In adhesion assays on frozen RA synovial sections, T lymphoblastoid cells expressing functionally activated alpha 4 beta 1 integrin specifically attached to the intravascular surface of RA endothelium. Binding was abrogated by both anti-alpha 4 integrin and CS1 peptides. Our observations suggest direct involvement of CS1-containing FN in recruitment of alpha 4 beta 1-expressing mononuclear leukocytes in synovitis, and provide basis for therapeutic intervention in RA.

Citing Articles

Get Spliced: Uniting Alternative Splicing and Arthritis.

van Haaren M, Steller L, Vastert S, Calis J, van Loosdregt J Int J Mol Sci. 2024; 25(15).

PMID: 39125692 PMC: 11311815. DOI: 10.3390/ijms25158123.

IL-1β stimulated human umbilical cord mesenchymal stem cells ameliorate rheumatoid arthritis via inducing apoptosis of fibroblast-like synoviocytes.

Chiu Y, Liang Y, Hwang J, Wang H Sci Rep. 2023; 13(1):15344.

PMID: 37714911 PMC: 10504325. DOI: 10.1038/s41598-023-42585-1.

FN1 is a prognostic biomarker and correlated with immune infiltrates in gastric cancers.

Wang H, Zhang J, Li H, Yu H, Chen S, Liu S Front Oncol. 2022; 12:918719.

PMID: 36081567 PMC: 9445423. DOI: 10.3389/fonc.2022.918719.

Splicing machinery is impaired in rheumatoid arthritis, associated with disease activity and modulated by anti-TNF therapy.

Ibanez-Costa A, Perez-Sanchez C, Patino-Trives A, Luque-Tevar M, Font P, Arias de la Rosa I Ann Rheum Dis. 2021; 81(1):56-67.

PMID: 34625402 PMC: 8762032. DOI: 10.1136/annrheumdis-2021-220308.

Photoacoustic microscopy: principles and biomedical applications.

Liu W, Yao J Biomed Eng Lett. 2019; 8(2):203-213.

PMID: 30603203 PMC: 6208522. DOI: 10.1007/s13534-018-0067-2.

References

Postigo A, Garcia-Vicuna R, Diaz-Gonzalez F, Arroyo A, de Landazuri M, Lobb R . Increased binding of synovial T lymphocytes from rheumatoid arthritis to endothelial-leukocyte adhesion molecule-1 (ELAM-1) and vascular cell adhesion molecule-1 (VCAM-1). J Clin Invest. 1992; 89(5):1445-52. PMC: 443014. DOI: 10.1172/JCI115734. View

Wayner E, Kovach N . Activation-dependent recognition by hematopoietic cells of the LDV sequence in the V region of fibronectin. J Cell Biol. 1992; 116(2):489-97. PMC: 2289302. DOI: 10.1083/jcb.116.2.489. View

Marlor C, Webb D, Bombara M, Greve J, BLUE M . Expression of vascular cell adhesion molecule-1 in fibroblastlike synoviocytes after stimulation with tumor necrosis factor. Am J Pathol. 1992; 140(5):1055-60. PMC: 1886511. View

Vonderheide R, Springer T . Lymphocyte adhesion through very late antigen 4: evidence for a novel binding site in the alternatively spliced domain of vascular cell adhesion molecule 1 and an additional alpha 4 integrin counter-receptor on stimulated endothelium. J Exp Med. 1992; 175(6):1433-42. PMC: 2119261. DOI: 10.1084/jem.175.6.1433. View

Roldan E, Garcia-Pardo A, Brieva J . VLA-4-fibronectin interaction is required for the terminal differentiation of human bone marrow cells capable of spontaneous and high rate immunoglobulin secretion. J Exp Med. 1992; 175(6):1739-47. PMC: 2119256. DOI: 10.1084/jem.175.6.1739. View

Osborn L, Vassallo C, Benjamin C . Activated endothelium binds lymphocytes through a novel binding site in the alternately spliced domain of vascular cell adhesion molecule-1. J Exp Med. 1992; 176(1):99-107. PMC: 2119269. DOI: 10.1084/jem.176.1.99. View

Wayner E, Elices M, Alvaro-Gracia J, Zvaifler N, Firestein G . Alpha 4/beta 1 integrin (VLA-4) ligands in arthritis. Vascular cell adhesion molecule-1 expression in synovium and on fibroblast-like synoviocytes. J Immunol. 1992; 149(4):1424-31. View

Masumoto A, Hemler M . Multiple activation states of VLA-4. Mechanistic differences between adhesion to CS1/fibronectin and to vascular cell adhesion molecule-1. J Biol Chem. 1993; 268(1):228-34. View

Grober J, Bowen B, EBLING H, Athey B, Thompson C, Fox D . Monocyte-endothelial adhesion in chronic rheumatoid arthritis. In situ detection of selectin and integrin-dependent interactions. J Clin Invest. 1993; 91(6):2609-19. PMC: 443325. DOI: 10.1172/JCI116500. View

10.

McLean I, Nakane P . Periodate-lysine-paraformaldehyde fixative. A new fixation for immunoelectron microscopy. J Histochem Cytochem. 1974; 22(12):1077-83. DOI: 10.1177/22.12.1077. View

11.

Butcher E . Leukocyte-endothelial cell recognition: three (or more) steps to specificity and diversity. Cell. 1991; 67(6):1033-6. DOI: 10.1016/0092-8674(91)90279-8. View

12.

van de Wiel-van Kemenade E, van Kooyk Y, de Boer A, Huijbens R, Weder P, van de Kasteele W . Adhesion of T and B lymphocytes to extracellular matrix and endothelial cells can be regulated through the beta subunit of VLA. J Cell Biol. 1992; 117(2):461-70. PMC: 2289428. DOI: 10.1083/jcb.117.2.461. View

13.

Stamper Jr H, Woodruff J . Lymphocyte homing into lymph nodes: in vitro demonstration of the selective affinity of recirculating lymphocytes for high-endothelial venules. J Exp Med. 1976; 144(3):828-33. PMC: 2190398. DOI: 10.1084/jem.144.3.828. View

14.

Jaffe E, Mosher D . Synthesis of fibronectin by cultured human endothelial cells. J Exp Med. 1978; 147(6):1779-91. PMC: 2184307. DOI: 10.1084/jem.147.6.1779. View

15.

Pierschbacher M, Hayman E, Ruoslahti E . Location of the cell-attachment site in fibronectin with monoclonal antibodies and proteolytic fragments of the molecule. Cell. 1981; 26(2 Pt 2):259-67. DOI: 10.1016/0092-8674(81)90308-1. View

16.

Schwarzbauer J, Tamkun J, Lemischka I, Hynes R . Three different fibronectin mRNAs arise by alternative splicing within the coding region. Cell. 1983; 35(2 Pt 1):421-31. DOI: 10.1016/0092-8674(83)90175-7. View

17.

Kornblihtt A, Baralle F . Human fibronectin: cell specific alternative mRNA splicing generates polypeptide chains differing in the number of internal repeats. Nucleic Acids Res. 1984; 12(14):5853-68. PMC: 320036. DOI: 10.1093/nar/12.14.5853. View

18.

Tamkun J, Schwarzbauer J, Hynes R . A single rat fibronectin gene generates three different mRNAs by alternative splicing of a complex exon. Proc Natl Acad Sci U S A. 1984; 81(16):5140-4. PMC: 391653. DOI: 10.1073/pnas.81.16.5140. View

19.

Sekiguchi K, Klos A, Kurachi K, Yoshitake S, Hakomori S . Human liver fibronectin complementary DNAs: identification of two different messenger RNAs possibly encoding the alpha and beta subunits of plasma fibronectin. Biochemistry. 1986; 25(17):4936-41. DOI: 10.1021/bi00365a032. View

20.

Magnusson S, Baralle F . Donor and acceptor splice signals within an exon of the human fibronectin gene: a new type of differential splicing. FEBS Lett. 1986; 207(2):287-91. DOI: 10.1016/0014-5793(86)81506-x. View