Connective tissue alterations in systemic sclerosis

TY - JOUR

T1 - Connective tissue alterations in systemic sclerosis

AU - Varga, John

AU - Rudnicka, Lidia

AU - Uitto, Jouni

N1 - Funding Information: Excessive deposition of connective tissue in the skin, lungs, heart, gastrointestinal tract, and other organs is the pathological hallmark of systemic sclerosis (SSc).l The uncontrolled accumulation of connective tissue results in disruption of normal tissue architecture, and ultimately leads to the dysfunction of the affected organs. The extracellular matrix, comprised of connective tissue macromolecules, fulfills a variety of vital functions. In addition to providing the structural framework for tissues, it mediates cell/cell and cell/matrix interactions and participates in cellular signaling by acting as a ligand binding site as well as a signal itself. During the past decade, it has become apparent that in addition to collagens, other components of the extracellular matrix are deposited in excessive amounts in SSc. The list of extracellular matrix components which are overexpressed in SSc includes several collagens (e.g., types I, III, IV, V, VI, and VII), as well as glycosaminoglycans (GAGS) and noncollage-nous glycoproteins, such as fibronectin, laminin, and tenascin. The excessive deposition of matrix components not only results in the characteristic tissue fibrosis of SSc but also plays an integral role in the pathogenesis of the disease. Although most recent evidence suggests that the accumulation of these macromolecules results from their overproduction by activated SSc fibroblasts, the signals responsible for this activation and the mechanisms involved are currently incompletely under- From the Deparfments of Medicine’, Dermatology? and Biochemistry and Molecular Biolo&, Jefferson Medical College, and Jefferson Institute of Molecular Medicine, Thomas Jefferson University, Philadelphia, PA 19107. Supported in part by the United States Public Health Service, National Institutes of Health Grants ROl-AR42309, ROl-41439, and T32-AR07561. Address for correspondence and requests for reprints: John Varga, M.D., Division of Rheumatology, Department of Medicine, Jefferson Medical College, 233 South 10th Street, Room 509, Philadelphia, PA 19107.

PY - 1994

Y1 - 1994

UR - http://www.scopus.com/inward/record.url?scp=0027934476&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0027934476&partnerID=8YFLogxK

U2 - 10.1016/0738-081X(94)90291-7

DO - 10.1016/0738-081X(94)90291-7

M3 - Article

C2 - 7525034

AN - SCOPUS:0027934476

SN - 0738-081X

VL - 12

SP - 387

EP - 396

JO - Clinics in Dermatology

JF - Clinics in Dermatology

IS - 3

ER -