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Full-Text Articles in Skin and Connective Tissue Diseases
Yap-Mediated Mechanotransduction Promotes Fibrotic Activity, Michael Racanelli
Yap-Mediated Mechanotransduction Promotes Fibrotic Activity, Michael Racanelli
Electronic Thesis and Dissertation Repository
Fibrosis, a phenotype associated with mortality for a multitude of diseases, has no disease-modifying treatment. We examine if Verteporfin (VP), an inhibitor of the YAP-TEAD complex, currently in wide clinical use for macular degeneration, can inhibit pro-fibrotic gene expression in human dermal fibroblasts. Also, an in vivo approach was taken using a Pten-deficient mouse of progressive skin fibrosis for examining effects on melanoma metastasis. We found that treatment with VP reduced basal expression of a variety of profibrotic genes and prevented a myofibroblast-like phenotype in response to TGFβ1. Indeed, genome-wide expression analysis suggested that VP inhibited a cluster of …
The Effect Of Function-Blocking Rhamm Peptides In A Mouse Model Of Bleomycin-Induced Systemic Sclerosis, Kitty Y. Wu
The Effect Of Function-Blocking Rhamm Peptides In A Mouse Model Of Bleomycin-Induced Systemic Sclerosis, Kitty Y. Wu
Electronic Thesis and Dissertation Repository
Systemic sclerosis is a chronic, fibrotic disorder associated with high disease-specific mortality and morbidity. Cutaneous manifestations include dermal thickening and obliteration of dermal adipose tissue. The efficacy of function-blocking Rhamm peptides, NPI-110 and NPI-106, were tested in reducing skin fibrosis and promoting adipogenesis in a bleomycin-induced mouse model of systemic sclerosis. NPI-110 reduced both visible measures of fibrosis (dermal thickness, collagen density, and fibril bundling) and mRNA expression of pro-fibrotic genes (Tgfb1, c-Myc, Col1a1, Col3a1). While there was no measurable change in dermal adipose thickness, NPI-110 treatment upregulated Perilipin mRNA and Adiponectin protein expression and is therefore hypothesized to …
Evaluation Of Matricellular Proteins As Potential Therapeutics For The Treatment Of Human Chronic Skin Wounds, Christopher G. Elliott
Evaluation Of Matricellular Proteins As Potential Therapeutics For The Treatment Of Human Chronic Skin Wounds, Christopher G. Elliott
Electronic Thesis and Dissertation Repository
There is currently an unmet need for treatments to enhance healing of human chronic skin wounds. Previously, therapy development has focused on growth factors and physical matrices, often resulting in disappointing clinical outcomes. In this thesis, we approached chronic skin wound treatment with a focus on fibrosis and matricellular proteins. Fibrosis is a pathological condition where tissue repair continues, unchecked, resulting in excess contraction, matrix accumulation and fibrogenic growth factor activity; features critically reduced in chronic skin wounds. Identifying factors that promote fibrosis may offer new therapeutic targets for use in chronic skin wounds. Two such factors are the matricellular …