Full Text Journal Articles by
Author Thomas H Sisson

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Diverse Injury Pathways Induce Alveolar Epithelial Cell CCL2/12, Which Promotes Lung Fibrosis.

Jibing Yang, Manisha Agarwal, Song Ling, Seagal Teitz-Tennenbaum, Rachel L Zemans, John J Osterholzer, Thomas H Sisson, Kevin K Kim,

Accumulating evidence suggests that fibrosis is a multicellular process with contributions from alveolar epithelial cells (AECs), recruited monocytes/macrophages, and fibroblasts. We have previously shown that AEC injury is sufficient to induce fibrosis, but the precise mechanism remains unclear. Several cell types, including AECs, can produce CCL2 and CCL12, which can ... Read more >>

Am J Respir Cell Mol Biol (American journal of respiratory cell and molecular biology)
[2020, 62(5):622-632]

Cited: 7 times

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Urokinase Plasminogen Activator Overexpression Reverses Established Lung Fibrosis.

Jeffrey C Horowitz, Daniel J Tschumperlin, Kevin K Kim, John J Osterholzer, Natalya Subbotina, Iyabode O Ajayi, Seagal Teitz-Tennenbaum, Ammara Virk, Megan Dotson, Fei Liu, Delphine Sicard, Shijing Jia, Thomas H Sisson,

INTRODUCTION: Impaired plasminogen activation (PA) is causally related to the development of lung fibrosis. Prior studies demonstrate that enhanced PA in the lung limits the severity of scarring following injury and in vitro studies indicate that PA promotes matrix degradation and fibroblast apoptosis. These findings led us to hypothesize that increased ... Read more >>

Thromb Haemost (Thrombosis and haemostasis)
[2019, 119(12):1968-1980]

Cited: 4 times

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Phosphodiesterase 4 inhibition reduces lung fibrosis following targeted type II alveolar epithelial cell injury.

Thomas H Sisson, Paul J Christensen, Yo Muraki, Anthony J Dils, Lauren Chibucos, Natalya Subbotina, Kimio Tohyama, Jeffrey C Horowitz, Takanori Matsuo, Marc Bailie, Sham Nikam, Masatoshi Hazama,

Fibrosis of the lung constitutes a major clinical challenge and novel therapies are required to alleviate the associated morbidity and mortality. Investigating the antifibrotic efficacy of drugs that are already in clinical practice offers an efficient strategy to identify new therapies. The phosphodiesterase 4 (PDE4) inhibitors, approved for the treatment ... Read more >>

Physiol Rep (Physiological reports)
[2018, 6(12):e13753]

Cited: 9 times

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Regulation of fibroblast Fas expression by soluble and mechanical pro-fibrotic stimuli.

Amos E Dodi, Iyabode O Ajayi, Christine Chang, Meghan Beard, Shanna L Ashley, Steven K Huang, Victor J Thannickal, Daniel J Tschumperlin, Thomas H Sisson, Jeffrey C Horowitz,

BACKGROUND:Fibroblast apoptosis is a critical component of normal repair and the acquisition of an apoptosis-resistant phenotype contributes to the pathogenesis of fibrotic repair. Fibroblasts from fibrotic lungs of humans and mice demonstrate resistance to apoptosis induced by Fas-ligand and prior studies have shown that susceptibility to apoptosis is enhanced when ... Read more >>

Respir Res (Respiratory research)
[2018, 19(1):91]

Cited: 10 times

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The influence of MCAT and GPA preadmission academic metrics on interview scores.

Steven E Gay, Sally A Santen, Rajesh S Mangrulkar, Thomas H Sisson, Paula T Ross, Nikki L Bibler Zaidi,

Medical school admissions interviews are used to assess applicants' nonacademic characteristics as advocated by the Association of American Medical Colleges' Advancing Holistic Review Initiative. The objective of this study is to determine whether academic metrics continue to significantly influence interviewers' scores in holistic processes by blinding interviewers to applicants' undergraduate ... Read more >>

Adv Health Sci Educ Theory Pract (Advances in health sciences education : theory and practice)
[2018, 23(1):151-158]

Cited: 0 times

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Fibroblast growth factors and pulmonary fibrosis: it's more complex than it sounds.

Kevin K Kim, Thomas H Sisson, Jeffrey C Horowitz,

Lung fibrosis results from the cumulative effect of dysfunctional wound repair involving multiple cell types, including fibroblasts, epithelial cells, and macrophages responding to an array of soluble and matrix-mediated stimuli. Recent studies have shown that a tyrosine kinase inhibitor that targets FGF, VEGF, and PDGF receptors can slow the rate ... Read more >>

J Pathol (The Journal of pathology)
[2017, 241(1):6-9]

Cited: 10 times

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Utility of Transbronchial vs Surgical Lung Biopsy in the Diagnosis of Suspected Fibrotic Interstitial Lung Disease.

Jamie S Sheth, John A Belperio, Michael C Fishbein, Ella A Kazerooni, Amir Lagstein, Susan Murray, Jeff L Myers, Richard H Simon, Thomas H Sisson, Baskaran Sundaram, Eric S White, Meng Xia, David Zisman, Kevin R Flaherty,

<h4>Background</h4>Surgical lung biopsy (SLB) is invasive and not possible in all patients with undiagnosed interstitial lung disease (ILD). We hypothesized that transbronchial biopsy (TBB) findings combined with clinical and high-resolution CT (HRCT) data leads to a confident diagnosis congruent to SLB and therefore avoids the need for SLB in some ... Read more >>

Chest (Chest)
[2017, 151(2):389-399]

Cited: 23 times

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Ultrasound Strain Measurements for Evaluating Local Pulmonary Ventilation.

Jonathan M Rubin, Jeffrey C Horowitz, Thomas H Sisson, Kang Kim, Luis A Ortiz, James D Hamilton,

Local lung function is difficult to evaluate, because most lung function estimates are either global in nature (e.g., pulmonary function tests) or require equipment that cannot be used at a patient's bedside, such as computed tomography. Yet, local function measurements would be highly desirable for many reasons. Recently, we were ... Read more >>

Ultrasound Med Biol (Ultrasound in medicine & biology)
[2016, 42(11):2525-2531]

Cited: 4 times

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Matriptase, Protease-activated Receptor 2, and Idiopathic Pulmonary Fibrosis. Further Evidence for Signaling Pathway Redundancy in this Difficult-to-Treat Disease?

Thomas H Sisson, Paolo Spagnolo,

Am J Respir Crit Care Med (American journal of respiratory and critical care medicine)
[2016, 193(8):816-817]

Cited: 1 time

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The vitronectin RGD motif regulates TGF-β-induced alveolar epithelial cell apoptosis.

Amanda K Wheaton, Miranda Velikoff, Manisha Agarwal, Tiffany T Loo, Jeffrey C Horowitz, Thomas H Sisson, Kevin K Kim,

Transforming growth factor-β (TGF-β) is a critical driver of acute lung injury and fibrosis. Injury leads to activation of TGF-β, which regulates changes in the cellular and matrix makeup of the lung during the repair and fibrosis phase. TGF-β can also initiate alveolar epithelial cell (AEC) apoptosis. Injury leads to ... Read more >>

Am J Physiol Lung Cell Mol Physiol (American journal of physiology. Lung cellular and molecular physiology)
[2016, 310(11):L1206-17]

Cited: 12 times

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Targeting Inhibitor of Apoptosis Proteins Protects from Bleomycin-Induced Lung Fibrosis.

Shanna L Ashley, Thomas H Sisson, Amanda K Wheaton, Kevin K Kim, Carol A Wilke, Iyabode O Ajayi, Natalya Subbotina, Shaomeng Wang, Colin S Duckett, Bethany B Moore, Jeffrey C Horowitz,

Accumulation of apoptosis-resistant fibroblasts is a hallmark of pulmonary fibrosis. We hypothesized that disruption of inhibitor of apoptosis protein (IAP) family proteins would limit lung fibrosis. We first show that transforming growth factor-β1 and bleomycin increase X-linked IAP (XIAP) and cellular IAP (cIAP)-1 and -2 in murine lungs and mesenchymal ... Read more >>

Am J Respir Cell Mol Biol (American journal of respiratory cell and molecular biology)
[2016, 54(4):482-492]

Cited: 25 times

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Ultrasound Strain Measurements for Evaluating Local Pulmonary Ventilation.

Jonathan M Rubin, Jeffrey C Horowitz, Thomas H Sisson, Kang Kim, Luis A Ortiz, James D Hamilton,

Local lung function is difficult to evaluate, because most lung function estimates are either global in nature, e.g. pulmonary function tests, or require equipment that cannot be used at a patient's bedside, such as computed tomograms. Yet, local function measurements would be highly desirable for many reasons. In a recent ... Read more >>

IEEE Int Ultrason Symp (IEEE International Ultrasonics Symposium : [proceedings]. IEEE International Ultrasonics Symposium)
[2015, 2015:]

Cited: 0 times

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Streptococcus pneumoniae triggers progression of pulmonary fibrosis through pneumolysin.

Sarah Knippenberg, Bianca Ueberberg, Regina Maus, Jennifer Bohling, Nadine Ding, Meritxell Tort Tarres, Heinz-Gerd Hoymann, Danny Jonigk, Nicole Izykowski, James C Paton, Abiodun D Ogunniyi, Sandro Lindig, Michael Bauer, Tobias Welte, Werner Seeger, Andreas Guenther, Thomas H Sisson, Jack Gauldie, Martin Kolb, Ulrich A Maus,

<h4>Rationale</h4>Respiratory tract infections are common in patients suffering from pulmonary fibrosis. The interplay between bacterial infection and fibrosis is characterised poorly.<h4>Objectives</h4>To assess the effect of Gram-positive bacterial infection on fibrosis exacerbation in mice.<h4>Methods</h4>Fibrosis progression in response to Streptococcus pneumoniae was examined in two different mouse models of pulmonary fibrosis.<h4>Measurements and ... Read more >>

Thorax (Thorax)
[2015, 70(7):636-646]

Cited: 31 times

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Milestones for Internal Medicine Sub-interns.

Sally A Santen, Jessica L Seidelman, Chad S Miller, Erica D Brownfield, Nathan Houchens, Thomas H Sisson, Monica L Lypson,

<h4>Background</h4>As residency programs move toward measuring milestones for competency-based education assessment, medical schools will need to collaborate with residencies to determine competencies for graduating students. The objective of this study is to define the educational milestones for fourth-year medical students during an Internal Medicine sub-internship.<h4>Methods</h4>A cross-sectional Internet-based survey (with attention ... Read more >>

Am J Med (The American journal of medicine)
[2015, 128(7):790-8.e2]

Cited: 6 times

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Future directions in idiopathic pulmonary fibrosis research. An NHLBI workshop report.

Timothy S Blackwell, Andrew M Tager, Zea Borok, Bethany B Moore, David A Schwartz, Kevin J Anstrom, Ziv Bar-Joseph, Peter Bitterman, Michael R Blackburn, William Bradford, Kevin K Brown, Harold A Chapman, Harold R Collard, Gregory P Cosgrove, Robin Deterding, Ramona Doyle, Kevin R Flaherty, Christine Kim Garcia, James S Hagood, Craig A Henke, Erica Herzog, Cory M Hogaboam, Jeffrey C Horowitz, Talmadge E King, James E Loyd, William E Lawson, Clay B Marsh, Paul W Noble, Imre Noth, Dean Sheppard, Julie Olsson, Luis A Ortiz, Thomas G O'Riordan, Tim D Oury, Ganesh Raghu, Jesse Roman, Patricia J Sime, Thomas H Sisson, Daniel Tschumperlin, Shelia M Violette, Timothy E Weaver, Rebecca G Wells, Eric S White, Naftali Kaminski, Fernando J Martinez, Thomas A Wynn, Victor J Thannickal, Jerry P Eu,

The median survival of patients with idiopathic pulmonary fibrosis (IPF) continues to be approximately 3 years from the time of diagnosis, underscoring the lack of effective medical therapies for this disease. In the United States alone, approximately 40,000 patients die of this disease annually. In November 2012, the NHLBI held ... Read more >>

Am J Respir Crit Care Med (American journal of respiratory and critical care medicine)
[2014, 189(2):214-222]

Cited: 128 times

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Increased survivin expression contributes to apoptosis-resistance in IPF fibroblasts.

Thomas H Sisson, Toby M Maher, Iyabode O Ajayi, Jessie E King, Peter D R Higgins, Adam J Booth, Rommel L Sagana, Steven K Huang, Eric S White, Bethany B Moore, Jeffrey C Horowitz,

Fibroblasts perform critical functions during the normal host response to tissue injury, but the inappropriate accumulation and persistent activation of these cells results in the development of tissue fibrosis. The mechanisms accounting for the aberrant accumulation of fibroblasts during fibrotic repair are poorly understood, although evidence supports a role for ... Read more >>

Adv Biosci Biotechnol (Advances in bioscience and biotechnology (Print))
[2012, 3(6A):657-664]

Cited: 39 times

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X-linked inhibitor of apoptosis regulates lung fibroblast resistance to Fas-mediated apoptosis.

Iyabode O Ajayi, Thomas H Sisson, Peter D R Higgins, Adam J Booth, Rommel L Sagana, Steven K Huang, Eric S White, Jessie E King, Bethany B Moore, Jeffrey C Horowitz,

The accumulation of apoptosis-resistant fibroblasts within fibroblastic foci is a characteristic feature of idiopathic pulmonary fibrosis (IPF), but the mechanisms underlying apoptosis resistance remain unclear. A role for the inhibitor of apoptosis (IAP) protein family member X-linked inhibitor of apoptosis (XIAP) has been suggested by prior studies showing that (1) ... Read more >>

Am J Respir Cell Mol Biol (American journal of respiratory cell and molecular biology)
[2013, 49(1):86-95]

Cited: 39 times

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Implicating exudate macrophages and Ly-6C(high) monocytes in CCR2-dependent lung fibrosis following gene-targeted alveolar injury.

John J Osterholzer, Michal A Olszewski, Benjamin J Murdock, Gwo-Hsiao Chen, John R Erb-Downward, Natalya Subbotina, Keely Browning, Yujing Lin, Roger E Morey, Jeremy K Dayrit, Jeffrey C Horowitz, Richard H Simon, Thomas H Sisson,

The alveolar epithelium is characteristically abnormal in fibrotic lung disease, and we recently established a direct link between injury to the type II alveolar epithelial cell (AEC) and the accumulation of interstitial collagen. The mechanisms by which damage to the epithelium induces lung scarring remain poorly understood. It is particularly ... Read more >>

J Immunol (Journal of immunology (Baltimore, Md. : 1950))
[2013, 190(7):3447-3457]

Cited: 63 times

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Survivin expression induced by endothelin-1 promotes myofibroblast resistance to apoptosis.

Jeffrey C Horowitz, Iyabode O Ajayi, Priya Kulasekaran, David S Rogers, Joshua B White, Sarah K Townsend, Eric S White, Richard S Nho, Peter D R Higgins, Steven K Huang, Thomas H Sisson,

Fibrosis of the lungs and other organs is characterized by the accumulation of myofibroblasts, effectors of wound-repair that are responsible for the deposition and organization of new extracellular matrix (ECM) in response to tissue injury. During the resolution phase of normal wound repair, myofibroblast apoptosis limits the continued deposition of ... Read more >>

Int J Biochem Cell Biol (The international journal of biochemistry & cell biology)
[2012, 44(1):158-169]

Cited: 48 times

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Plasmin overcomes resistance to prostaglandin E2 in fibrotic lung fibroblasts by reorganizing protein kinase A signaling.

Katsuhide Okunishi, Thomas H Sisson, Steven K Huang, Cory M Hogaboam, Richard H Simon, Marc Peters-Golden,

Collagen deposition by fibroblasts contributes to scarring in fibrotic diseases. Activation of protein kinase A (PKA) by cAMP represents a pivotal brake on fibroblast activation, and the lipid mediator prostaglandin E(2) (PGE(2)) exerts its well known anti-fibrotic actions through cAMP signaling. However, fibrotic fibroblasts from the lungs of patients with ... Read more >>

J Biol Chem (The Journal of biological chemistry)
[2011, 286(37):32231-32243]

Cited: 16 times

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Macrophage-specific expression of urokinase-type plasminogen activator promotes skeletal muscle regeneration.

Margaret L Novak, Scott C Bryer, Ming Cheng, Mai-Huong Nguyen, Kevin L Conley, Andrew K Cunningham, Bing Xue, Thomas H Sisson, Jae-Sung You, Troy A Hornberger, Timothy J Koh,

Macrophages (Mp) and the plasminogen system play important roles in tissue repair following injury. We hypothesized that Mp-specific expression of urokinase-type plasminogen activator (uPA) is sufficient for Mp to migrate into damaged muscle and for efficient muscle regeneration. We generated transgenic mice expressing uPA only in Mp, and we assessed ... Read more >>

J Immunol (Journal of immunology (Baltimore, Md. : 1950))
[2011, 187(3):1448-1457]

Cited: 24 times

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Urokinase-type plasminogen activator increases hepatocyte growth factor activity required for skeletal muscle regeneration.

Thomas H Sisson, Mai-Huong Nguyen, Bi Yu, Margaret L Novak, Richard H Simon, Timothy J Koh,

The plasminogen system plays a crucial role in the repair of a variety of tissues, including skeletal muscle. We hypothesized that urokinase-type plasminogen activator (uPA) promotes muscle regeneration by activating hepatocyte growth factor (HGF), which, in turn, stimulates proliferation of myoblasts required for regeneration. In our studies, levels of active ... Read more >>

Blood (Blood)
[2009, 114(24):5052-5061]

Cited: 31 times

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The antifibrotic effects of plasminogen activation occur via prostaglandin E2 synthesis in humans and mice.

Kristy A Bauman, Scott H Wettlaufer, Katsuhide Okunishi, Kevin M Vannella, Joshua S Stoolman, Steven K Huang, Anthony J Courey, Eric S White, Cory M Hogaboam, Richard H Simon, Galen B Toews, Thomas H Sisson, Bethany B Moore, Marc Peters-Golden,

Plasminogen activation to plasmin protects from lung fibrosis, but the mechanism underlying this antifibrotic effect remains unclear. We found that mice lacking plasminogen activation inhibitor-1 (PAI-1), which are protected from bleomycin-induced pulmonary fibrosis, exhibit lung overproduction of the antifibrotic lipid mediator prostaglandin E2 (PGE2). Plasminogen activation upregulated PGE2 synthesis in ... Read more >>

J Clin Invest (The Journal of clinical investigation)
[2010, 120(6):1950-1960]

Cited: 85 times

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Inhalation of urokinase-type plasminogen activator reduces airway remodeling in a murine asthma model.

Emi Kuramoto, Teruaki Nishiuma, Kazuyuki Kobayashi, Masatsugu Yamamoto, Yuko Kono, Yasuhiro Funada, Yoshikazu Kotani, Thomas H Sisson, Richard H Simon, Yoshihiro Nishimura,

The airway remodeling that occurs in asthma is characterized by an excess of extracellular matrix deposition in the submucosa, hyperplasia/hypertrophy of smooth muscle, goblet cell metaplasia, and accumulation of fibroblasts/myofibroblasts. The urokinase-type plasminogen activator (uPA)/plasmin system participates in pericellular proteolysis and is capable of directly degrading matrix components, activating latent ... Read more >>

Am J Physiol Lung Cell Mol Physiol (American journal of physiology. Lung cellular and molecular physiology)
[2009, 296(3):L337-46]

Cited: 24 times

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Plasminogen activation induced pericellular fibronectin proteolysis promotes fibroblast apoptosis.

Jeffrey C Horowitz, David S Rogers, Richard H Simon, Thomas H Sisson, Victor J Thannickal,

Apoptosis of fibroblasts/myofibroblasts is a critical event in the resolution of tissue repair responses; however, mechanisms for the regulation of (myo)fibroblast apoptosis/survival remain unclear. In this study, we demonstrate counter-regulatory interactions between the plasminogen activation system and transforming growth factor-beta1 (TGF-beta1) in the control of fibroblast apoptosis. Plasmin treatment induced ... Read more >>

Am J Respir Cell Mol Biol (American journal of respiratory cell and molecular biology)
[2008, 38(1):78-87]

Cited: 62 times

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