Logan Mlakar

Ameliorating Fibrosis in Murine and Human Tissues with END55, an Endostatin-Derived Fusion Protein Made in Plants

Logan Mlakar, Sara M. Garrett, Tomoya Watanabe, Matthew Sanderson et autres

Organ fibrosis, particularly of the lungs, causes significant morbidity and mortality. Effective treatments are needed to reduce the health burden. A fragment of the carboxyl-terminal end of collagen XVIII/endostatin reduces skin and lung fibrosis. This fragment was modified to facilitate its production …

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E4 engages uPAR and enolase-1 and activates urokinase to exert antifibrotic effects

Shailza Sharma, Tomoya Watanabe, Tetsuya NISHIMOTO, Takahisa Takihara et autres

Fibroproliferative disorders such as systemic sclerosis (SSc) have no effective therapies and result in significant morbidity and mortality. We recently demonstrated that the C-terminal domain of endostatin, known as E4, prevented and reversed both dermal and pulmonary fibrosis. Our goal was to …

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Lysyl oxidase directly contributes to extracellular matrix production and fibrosis in systemic sclerosis

Xinh-Xinh Nguyen, Tetsuya NISHIMOTO, Takahisa Takihara, Logan Mlakar et autres

Pulmonary fibrosis is one of the important causes of morbidity and mortality in fibroproliferative disorders such as systemic sclerosis (SSc) and idiopathic pulmonary fibrosis (IPF). Lysyl oxidase (LOX) is a copper-dependent amine oxidase whose primary function is the covalent crosslinking of collagens …

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Oxetanyl Sulfoxide MMS-350 Ameliorates Pulmonary Fibrosis In Vitro, In Vivo, and Ex Vivo

Logan Mlakar, Jessica R. Lane, Takahisa Takihara, Chaemin Lim et autres

Fibrosis is a common feature of several diseases, involves different organs, and results in significant morbidity and mortality. There are currently no effective therapies to halt the progression of fibrosis or reverse it. We have identified the highly water-soluble MMS-350, a novel …

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A Human Skin Model Recapitulates Systemic Sclerosis Dermal Fibrosis and Identifies COL22A1 as a TGFβ Early Response Gene that Mediates Fibroblast to Myofibroblast Transition

Tomoya Watanabe, DeAnna Baker Frost, Logan Mlakar, Jonathan Heywood et autres

Systemic sclerosis (SSc) is a complex multi-system autoimmune disease characterized by immune dysregulation, vasculopathy, and organ fibrosis. Skin fibrosis causes high morbidity and impaired quality of life in affected individuals. Animal models do not fully recapitulate the human disease. Thus, there is …

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2027 The role of lysyl oxidase in systemic sclerosis-associated lung fibrosis

Xinh-Xinh Nguyen, Tetsuya NISHIMOTO, Takahisa Takihara, Logan Mlakar et autres

OBJECTIVES/SPECIFIC AIMS: Systemic sclerosis (SSc) is a connective tissue disease of unknown etiology characterized by progressive fibrosis of the skin and multiple visceral organs. Effective therapies for SSc are needed. Lysyl oxidase (LOX) is a copper-dependent amide oxidase that plays a critical …

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Optimization of a murine and human tissue model to recapitulate dermal and pulmonary features of systemic sclerosis

Tomoya Watanabe, Tetsuya NISHIMOTO, Logan Mlakar, Jonathan Heywood et autres

The murine bleomycin (BLM)-induced fibrosis model is the most widely used in systemic sclerosis (SSc) studies. It has been reported that systemic delivery of BLM via continuous diffusion from subcutaneously implanted osmotic minipumps can cause fibrosis of the skin, lungs, and other …

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An endostatin-derived peptide orally exerts anti-fibrotic activity in a murine pulmonary fibrosis model

Tetsuya NISHIMOTO, Logan Mlakar, Takahisa Takihara, Carol A. Feghali‐Bostwick

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The cardiac regenerative potential of myoblasts remains limited despite improving their survival via antioxidant treatment.

Beckman Sa, Naosumi Sekiya, Logan Mlakar, Kimimasa Tobita et autres

INTRODUCTION: Since myoblasts have been limited by poor cell survival after cellular myoplasty, the major goal of the current study was to determine whether improving myoblast survival with an antioxidant could improve cardiac function after the transplantation of the myoblasts into an …

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Interferon-gamma inducible protein-10 as a potential biomarker in localized scleroderma

Kelsey E. Magee, Christina Kelsey, Katherine L. Kurzinski, Jonhan Ho et autres

INTRODUCTION: The purpose of this study was to evaluate the presence and levels of interferon-gamma inducible protein-10 (IP-10) in the plasma and skin of pediatric localized scleroderma (LS) patients compared to those of healthy pediatric controls and to determine if IP-10 levels …

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Beneficial Effect of Mechanical Stimulation on the Regenerative Potential of Muscle-Derived Stem Cells Is Lost by Inhibiting Vascular Endothelial Growth Factor

Sarah Beckman, Ying Margie Tang, Jonathan D. Proto, Logan Mlakar et autres

OBJECTIVE: We previously reported that mechanical stimulation increased the effectiveness of muscle-derived stem cells (MDSCs) for tissue repair. The objective of this study was to determine the importance of vascular endothelial growth factor (VEGF) on mechanically stimulated MDSCs in a murine model …

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Syndecan-2 Is a Novel Target of Insulin-Like Growth Factor Binding Protein-3 and Is Over-Expressed in Fibrosis

Ximena D. Ruiz, Logan Mlakar, Yukie Yamaguchi, Yunyun Su et autres

Extracellular matrix deposition and tissue scarring characterize the process of fibrosis. Transforming growth factor beta (TGFβ) and Insulin-like growth factor binding protein-3 (IGFBP-3) have been implicated in the pathogenesis of fibrosis in various tissues by inducing mesenchymal cell proliferation and extracellular matrix …

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