Medicine and Health Sciences Commons^™

Caveolin-1, Tgf-Β Receptor Internalization, And The Pathogenesis Of Systemic Sclerosis, Francesco Del Galdo, Michael P. Lisanti, Sergio A. Jimenez

Jefferson Institute of Molecular Medicine Papers and Presentations

PURPOSE OF REVIEW: To review the scientific literature supporting the participation of caveolin-1 in the pathogenesis of tissue fibrosis and the notion that modulation of the caveolin-1 pathway may represent a novel treatment for systemic sclerosis and other fibrotic diseases.

RECENT FINDINGS: Caveolin-1 plays an important role in the regulation of transforming growth factor-beta (TGF-beta) signaling owing to its participation in TGF-beta receptor internalization. TGF-beta receptor internalized through caveolin-1 lipid rafts undergoes rapid degradation, effectively decreasing TGF-beta signaling. Studies have shown that caveolin-1 knockdown in vitro markedly increased collagen gene expression in normal human lung fibroblasts. Caveolin-1 was reduced in …

Decreased Expression Of Caveolin 1 In Patients With Systemic Sclerosis: Crucial Role In The Pathogenesis Of Tissue Fibrosis., Francesco Del Galdo, Federica Sotgia, Cecilia J. De Almeida, Jean-Francois Jasmin, Megan Musick, Michael P. Lisanti, Sergio A. Jimenez

Department of Medicine Faculty Papers

OBJECTIVE: Recent studies have implicated caveolin 1 in the regulation of transforming growth factor beta (TGFbeta) downstream signaling. Given the crucial role of TGFbeta in the pathogenesis of systemic sclerosis (SSc), we sought to determine whether caveolin 1 is also involved in the pathogenesis of tissue fibrosis in SSc. We analyzed the expression of CAV1 in affected SSc tissues, studied the effects of lack of expression of CAV1 in vitro and in vivo, and analyzed the effects of restoration of caveolin 1 function on the fibrotic phenotype of SSc fibroblasts in vitro.

METHODS: CAV1 expression in tissues was analyzed by …

Molecular Ablation Of Transforming Growth Factor Beta Signaling Pathways By Tyrosine Kinase Inhibition: The Coming Of A Promising New Era In The Treatment Of Tissue Fibrosis., Joel Rosenbloom, Sergio A. Jimenez

Department of Medicine Faculty Papers

No abstract provided.

Targeting Nf-Kappab: A Promising Molecular Therapy In Inflammatory Arthritis., Jorge A. Roman-Blas, Sergio A. Jimenez

Scleroderma Center Faculty Papers

The nuclear factor-kappa B family of transcription factors is intimately involved in the regulation of the inflammatory responses that play a fundamental role in the damage of articular tissues. Thus, many studies have examined the important contributions of components of the NF-kappaB signaling pathways to the pathogenesis of various rheumatic diseases and their pharmacologic modulation. Currently available therapeutic agents including nonsteroidal anti-inflammatory drugs, corticosteroids, nutraceuticals, and disease-modifying antirheumatic drugs, as well as novel specific small-molecule inhibitors have been employed. In addition, promising nucleic acid-based strategies have shown encouraging results. However, further research will be needed before NF-kappaB-aimed strategies become an …

Elucidating A Normal Function Of Huntingtin By Functional And Microarray Analysis Of Huntingtin-Null Mouse Embryonic Fibroblasts., Hua Zhang, Sudipto Das, Quan-Zhen Li, Ioannis Dragatsis, Joyce Repa, Scott Zeitlin, György Hajnóczky, Ilya Bezprozvanny

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

BACKGROUND: The polyglutamine expansion in huntingtin (Htt) protein is a cause of Huntington's disease (HD). Htt is an essential gene as deletion of the mouse Htt gene homolog (Hdh) is embryonic lethal in mice. Therefore, in addition to elucidating the mechanisms responsible for polyQ-mediated pathology, it is also important to understand the normal function of Htt protein for both basic biology and for HD. RESULTS: To systematically search for a mouse Htt function, we took advantage of the Hdh +/- and Hdh-floxed mice and generated four mouse embryonic fibroblast (MEF) cells lines which contain a single copy of the Hdh …