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Full-Text Articles in Skin and Connective Tissue Diseases

Adipocytes And Innate Immunity In Systemic Sclerosis, Nancy Wareing May 2023

Adipocytes And Innate Immunity In Systemic Sclerosis, Nancy Wareing

Dissertations & Theses (Open Access)

Systemic sclerosis (SSc; scleroderma) is a chronic systemic autoimmune and connective tissue disorder characterized by vasculopathy, autoimmune phenomena, and widespread fibrosis. Skin thickening and tightening is the cardinal feature of SSc and is responsible, in part, for the considerable morbidity of this disease. There are currently no targeted treatments for skin manifestations in SSc, primarily due to our fragmented understanding of its pathophysiologic mechanisms. In PART I, we report a previously unappreciated link between aberrant expression of the developmental gene sine oculis homeobox homolog 1 (SIX1) in skin-associated adipocytes in SSc skin and the early loss of dermal white adipose …


Incorporation Of Lignin In Natural And Synthetic Biomaterials To Alter Mechanical And Biochemical Properties For Enhanced Wound Healing, Jorge Alfonso Belgodere Nov 2020

Incorporation Of Lignin In Natural And Synthetic Biomaterials To Alter Mechanical And Biochemical Properties For Enhanced Wound Healing, Jorge Alfonso Belgodere

LSU Doctoral Dissertations

It is estimated that chronic, non-healing wounds affect more than 6.5 million Americans annually, with an estimated healthcare cost beyond $14 billion. Here, we attempted to create composites of natural (collagen type I or gelatin-methacrylate) or synthetic (poly(ethylene glycol) polymers incorporating a natural plant component, lignin, to combat the costs and limitations current wound healing methods face. Three-dimensional matrices of collagen type I (Col I) are widely used in tissue engineering applications for its abundance in many tissues, bioactivity with many cell types, and excellent biocompatibility. Inspired by the structural role of lignin in plant tissue, we found that sodium …


Yap-Mediated Mechanotransduction Promotes Fibrotic Activity, Michael Racanelli Jun 2019

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 Nov 2018

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 Aug 2013

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 …