Skin and Connective Tissue Diseases Commons^™

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 …

Trametinib-Induced Epidermal Thinning Accelerates A Mouse Model Of Junctional Epidermolysis Bullosa, Grace Tartaglia, Pyung Hung Park, Michael H. Alexander, Alexander Nyström, Joel Rosenbloom, Andrew P. South

Department of Dermatology and Cutaneous Biology Faculty Papers

Junctional epidermolysis bullosa (JEB) patients experience skin and epithelial fragility due to a pathological deficiency in genes associated with epidermal adhesion. Disease severity ranges from post-natal lethality to localized skin involvement with persistent blistering followed by granulation tissue formation and atrophic scarring. We evaluated the potential of utilizing Trametinib, an MEK inhibitor previously shown to target fibrosis, with and without the documented EB-anti-fibrotic Losartan for reducing disease severity in a mouse model of JEB; Lamc2jeb mice. We found that Trametinib treatment accelerated disease onset and decreased epidermal thickness, which was in large part ameliorated by Losartan treatment. Interestingly, a range …

Establishment Of An In Vivo Streptozotocin-Induced Type 1 Diabetes Model Recapitulating Early Brain And Retinal Fibrosis, Kia Bourdot, Lucy Dawson, Igor Kuzin, Arturo Bravo Nuevo, Zeus Antonello

Cooper Rowan Medical Journal

INTRODUCTION: Diabetes has risen to one of the top American public health concerns. The hyperglycemic state of chronic diabetes leads to microvascular and macrovascular changes that predispose patients to delayed wound healing and organ fibrosis. The validation of models to specifically detect early, quantifiable fibrotic changes seen in the diabetic state is of fundamental importance for understanding the diabetic pathophysiology and exploring earlier management options. Here, we investigated if we could detect early signs of internal fibrosis in a streptozotocin (STZ) diabetic mouse model by quantifying α-SMA expression in various organs using flow cytometry.

METHODS: We used a low-dose STZ-induced …

Rna Isolation In Duchenne Muscular Dystrophy (Dmd) Mice Models, Salem Abu Al-Burak

Undergraduate Student Research Internships Conference

Fibrosis is a progressive and typically irreversible disease process characterized by the excessive deposition of collagen in organs and in tissues of the musculoskeletal (MSK) system^1,2. This process, which causes loss of organ and tissue function, can be initiated by micro-traumas³, an excessive and/or prolonged immune response¹, the activation and proliferation of fibrosis-inducing progenitor cells⁴, and a pro-fibrotic extra-cellular microenvironment⁵. In parallel with the events that initiate fibrosis, genetic or environmental influences may cause cells and tissues to become predisposed to fibrosis development prior to initiation. This suggests that these …

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

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

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

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 …