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  1. Article ; Online: Correction to "Inhibition of hyaluronan synthesis attenuates pulmonary hypertension associated with lung fibrosis".

    Karmouty-Quintana, Harry

    British journal of pharmacology

    2023  Volume 180, Issue 19, Page(s) 2599

    Language English
    Publishing date 2023-07-25
    Publishing country England
    Document type Published Erratum
    ZDB-ID 80081-8
    ISSN 1476-5381 ; 0007-1188
    ISSN (online) 1476-5381
    ISSN 0007-1188
    DOI 10.1111/bph.16194
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Book ; Online: Molecular Mechanisms in Pulmonary Hypertension and Right Ventricle Dysfunction

    Karmouty-Quintana, Harry / Guignabert, Christophe / Kwapiszewska, Grazyna / Ormiston, Mark L.

    2019  

    Keywords Science: general issues ; Physiology ; vascular remodeling ; Smooth Muscle Cell ; endothelial cell ; hypoxia ; Fibrosis ; pulmonary arterial hypertension ; Mitochondria ; Bleomycin ; Inflammation ; Iron
    Size 1 electronic resource (170 pages)
    Publisher Frontiers Media SA
    Document type Book ; Online
    Note English ; Open Access
    HBZ-ID HT021229848
    ISBN 9782889457731 ; 2889457737
    Database ZB MED Catalogue: Medicine, Health, Nutrition, Environment, Agriculture

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  3. Article ; Online: Snakes and Ladders: A Potential Therapy of Hepatocyte Growth Factor and Pigment Epithelium-derived Factor in Pulmonary Hypertension.

    Zambelas, Joseph M / Karmouty-Quintana, Harry

    American journal of respiratory cell and molecular biology

    2023  Volume 69, Issue 1, Page(s) 10–12

    MeSH term(s) Humans ; Animals ; Hepatocyte Growth Factor/metabolism ; Hypertension, Pulmonary/metabolism ; Eye Proteins ; Serpins ; Snakes/metabolism
    Chemical Substances Hepatocyte Growth Factor (67256-21-7) ; pigment epithelium-derived factor ; Eye Proteins ; Serpins
    Language English
    Publishing date 2023-05-11
    Publishing country United States
    Document type Editorial ; Research Support, N.I.H., Extramural ; Comment
    ZDB-ID 1025960-0
    ISSN 1535-4989 ; 1044-1549
    ISSN (online) 1535-4989
    ISSN 1044-1549
    DOI 10.1165/rcmb.2023-0118ED
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    Zs.A 2851: Show issues Location:
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  4. Article ; Online: Crystal Deposits in Macrophages and Distal Lung Remodeling: A Tale of Aging in SFTPC-Deficient Mice.

    Weng, Tingting / Karmouty-Quintana, Harry

    American journal of respiratory cell and molecular biology

    2020  Volume 62, Issue 4, Page(s) 405–406

    MeSH term(s) Aging ; Animals ; Cholesterol ; Lung ; Macrophages ; Mice ; Protein C ; Surface-Active Agents
    Chemical Substances Protein C ; Surface-Active Agents ; Cholesterol (97C5T2UQ7J)
    Language English
    Publishing date 2020-01-28
    Publishing country United States
    Document type Editorial ; Comment
    ZDB-ID 1025960-0
    ISSN 1535-4989 ; 1044-1549
    ISSN (online) 1535-4989
    ISSN 1044-1549
    DOI 10.1165/rcmb.2020-0018ED
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  5. Article ; Online: The emerging role of NOTCH3 receptor signalling in human lung diseases.

    Bodas, Manish / Subramaniyan, Bharathiraja / Karmouty-Quintana, Harry / Vitiello, Peter F / Walters, Matthew S

    Expert reviews in molecular medicine

    2022  Volume 24, Page(s) e33

    Abstract: The mammalian respiratory system or lung is a tree-like branching structure, and the main site of gas exchange with the external environment. Structurally, the lung is broadly classified into the proximal (or conducting) airways and the distal alveolar ... ...

    Abstract The mammalian respiratory system or lung is a tree-like branching structure, and the main site of gas exchange with the external environment. Structurally, the lung is broadly classified into the proximal (or conducting) airways and the distal alveolar region, where the gas exchange occurs. In parallel with the respiratory tree, the pulmonary vasculature starts with large pulmonary arteries that subdivide rapidly ending in capillaries adjacent to alveolar structures to enable gas exchange. The NOTCH signalling pathway plays an important role in lung development, differentiation and regeneration post-injury. Signalling via the NOTCH pathway is mediated through activation of four NOTCH receptors (NOTCH1-4), with each receptor capable of regulating unique biological processes. Dysregulation of the NOTCH pathway has been associated with development and pathophysiology of multiple adult acute and chronic lung diseases. This includes accumulating evidence that alteration of NOTCH3 signalling plays an important role in the development and pathogenesis of chronic obstructive pulmonary disease, lung cancer, asthma, idiopathic pulmonary fibrosis and pulmonary arterial hypertension. Herein, we provide a comprehensive summary of the role of NOTCH3 signalling in regulating repair/regeneration of the adult lung, its association with development of lung disease and potential therapeutic strategies to target its signalling activity.
    MeSH term(s) Animals ; Biological Phenomena ; Humans ; Lung Diseases ; Mammals/metabolism ; Receptor, Notch3/genetics ; Receptor, Notch3/metabolism ; Receptors, Notch/genetics ; Receptors, Notch/metabolism ; Signal Transduction
    Chemical Substances NOTCH3 protein, human ; Receptor, Notch3 ; Receptors, Notch
    Language English
    Publishing date 2022-09-02
    Publishing country England
    Document type Journal Article ; Review
    ISSN 1462-3994
    ISSN (online) 1462-3994
    DOI 10.1017/erm.2022.27
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Hyaluronan in the pathogenesis of acute and post-acute COVID-19 infection.

    Barnes, Henry W / Demirdjian, Sally / Haddock, Naomi L / Kaber, Gernot / Martinez, Hunter A / Nagy, Nadine / Karmouty-Quintana, Harry / Bollyky, Paul L

    Matrix biology : journal of the International Society for Matrix Biology

    2023  Volume 116, Page(s) 49–66

    Abstract: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) recently emerged as the cause of a global pandemic. Infection with SARS-CoV-2 can result in COVID-19 with both acute and chronic disease manifestations that continue to impact many patients ... ...

    Abstract Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) recently emerged as the cause of a global pandemic. Infection with SARS-CoV-2 can result in COVID-19 with both acute and chronic disease manifestations that continue to impact many patients long after the resolution of viral replication. There is therefore great interest in understanding the host factors that contribute to COVID-19 pathogenesis. In this review, we address the role of hyaluronan (HA), an extracellular matrix polymer with roles in inflammation and cellular metabolism, in COVID-19 and critically evaluate the hypothesis that HA promotes COVID-19 pathogenesis. We first provide a brief overview of COVID-19 infection. Then we briefly summarize the known roles of HA in airway inflammation and immunity. We then address what is known about HA and the pathogenesis of COVID-19 acute respiratory distress syndrome (COVID-19 ARDS). Next, we examine potential roles for HA in post-acute SARS-CoV-2 infection (PASC), also known as "long COVID" as well as in COVID-associated fibrosis. Finally, we discuss the potential therapeutics that target HA as a means to treat COVID-19, including the repurposed drug hymecromone (4-methylumbelliferone). We conclude that HA is a promising potential therapeutic target for the treatment of COVID-19.
    MeSH term(s) Humans ; COVID-19 ; SARS-CoV-2 ; Hyaluronic Acid ; Inflammation/pathology ; Post-Acute COVID-19 Syndrome
    Chemical Substances Hyaluronic Acid (9004-61-9)
    Language English
    Publishing date 2023-02-05
    Publishing country Netherlands
    Document type Journal Article ; Review ; Research Support, N.I.H., Extramural
    ZDB-ID 1183793-7
    ISSN 1569-1802 ; 0945-053X
    ISSN (online) 1569-1802
    ISSN 0945-053X
    DOI 10.1016/j.matbio.2023.02.001
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    Zs.A 1694: Show issues Location:
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  7. Article ; Online: STAT6 suppression prevents bleomycin-induced dermal fibrosis.

    Huang, Jingjing / Puente, Hydia / Wareing, Nancy E / Wu, Minghua / Mayes, Maureen D / Karmouty-Quintana, Harry / Assassi, Shervin / Mills, Tingting W

    FASEB journal : official publication of the Federation of American Societies for Experimental Biology

    2023  Volume 37, Issue 2, Page(s) e22761

    Abstract: Fibrosis of the skin and internal organs is a hallmark of systemic sclerosis (SSc). Although the pathogenesis of SSc is poorly understood, increasing evidence suggests that interleukins (IL)-4 and - 13 contribute to the pathogenesis of skin fibrosis by ... ...

    Abstract Fibrosis of the skin and internal organs is a hallmark of systemic sclerosis (SSc). Although the pathogenesis of SSc is poorly understood, increasing evidence suggests that interleukins (IL)-4 and - 13 contribute to the pathogenesis of skin fibrosis by promoting collagen production and myofibroblast differentiation. Signal transducers and activators of transcription 6 (STAT6) is one of the most important downstream transcription factors activated by both IL-4 and IL-13. However, it is not completely understood whether STAT6 plays a role during the pathogenesis of skin fibrosis in SSc. In this study, we observed increased STAT6 phosphorylation in fibrotic skin samples collected from SSc patients as well as bleomycin-injected murine mice. Knockout of Stat6 in mice significantly (1) suppressed the expression of fibrotic cytokines including Il13, Il17, Il22, Ccl2, and the alternatively activated macrophage marker Cd206; (2) reduced the production of collagen and fibronectin, and (3) attenuated late-stage skin fibrosis and inflammation induced by bleomycin. Consistently, mice treated with STAT6 inhibitor AS1517499 also attenuated skin fibrosis on day 28. In addition, a co-culture experiment demonstrated that skin epithelial cells with STAT6 knockdown had reduced cytokine expression in response to IL-4/IL-13, and subsequently attenuated fibrotic protein expression in skin fibroblasts. On the other side, STAT6 depletion in skin fibroblasts attenuated IL-4/IL-13-induced cytokine and fibrotic marker expression, and reduced CXCL2 expression in co-cultured keratinocytes. In summary, our study highlighted an important yet not fully understood role of STAT6 in skin fibrosis by driving innate inflammation and differentiation of alternatively activated macrophages in response to injury.
    MeSH term(s) Animals ; Mice ; Bleomycin/toxicity ; Interleukin-4/genetics ; Interleukin-4/metabolism ; Interleukin-13/genetics ; Interleukin-13/metabolism ; Mice, Knockout ; Fibrosis ; Scleroderma, Systemic/chemically induced ; Scleroderma, Systemic/genetics ; Scleroderma, Systemic/metabolism ; Collagen/metabolism ; Fibroblasts/metabolism ; Inflammation/metabolism ; Skin/metabolism ; Disease Models, Animal ; STAT6 Transcription Factor/genetics ; STAT6 Transcription Factor/metabolism
    Chemical Substances Bleomycin (11056-06-7) ; Interleukin-4 (207137-56-2) ; Interleukin-13 ; Collagen (9007-34-5) ; Stat6 protein, mouse ; STAT6 Transcription Factor
    Language English
    Publishing date 2023-01-10
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
    ZDB-ID 639186-2
    ISSN 1530-6860 ; 0892-6638
    ISSN (online) 1530-6860
    ISSN 0892-6638
    DOI 10.1096/fj.202200994R
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    Zs.A 2266: Show issues Location:
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    Zs.MO 296: Show issues

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  8. Article: Mechanisms of Pulmonary Hypertension in Acute Respiratory Distress Syndrome (ARDS).

    Revercomb, Lucy / Hanmandlu, Ankit / Wareing, Nancy / Akkanti, Bindu / Karmouty-Quintana, Harry

    Frontiers in molecular biosciences

    2021  Volume 7, Page(s) 624093

    Abstract: Background: ...

    Abstract Background:
    Language English
    Publishing date 2021-01-18
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2814330-9
    ISSN 2296-889X
    ISSN 2296-889X
    DOI 10.3389/fmolb.2020.624093
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  9. Article ; Online: Cleavage stimulating factor 64 depletion mitigates cardiac fibrosis through alternative polyadenylation.

    Neupane, Rahul / Youker, Keith / Yalamanchili, Hari Krishna / Cieslik, Katarzyna A / Karmouty-Quintana, Harry / Guha, Ashrith / Thandavarayan, Rajarajan A

    Biochemical and biophysical research communications

    2022  Volume 597, Page(s) 109–114

    Abstract: Alternative polyadenylation (APA) regulates gene expression by cleavage and addition of poly(A) sequence at different polyadenylation sites (PAS) in 3'UTR, thus, generating transcript isoforms with different lengths. Cleavage stimulating factor 64 ( ... ...

    Abstract Alternative polyadenylation (APA) regulates gene expression by cleavage and addition of poly(A) sequence at different polyadenylation sites (PAS) in 3'UTR, thus, generating transcript isoforms with different lengths. Cleavage stimulating factor 64 (CstF64) is an APA regulator which plays a role in PAS selection and determines the length of 3'UTR. CstF64 favors the use of proximal PAS, resulting in 3'UTR shortening, which enhances the protein expression by increasing the stability of the target genes. The aim of this study is to investigate the role of CstF64 in cardiac fibrosis, a key event leading to heart failure (HF). We determined the expression of CstF64, key profibrotic genes, and their 3'UTR changes by calculating distal PAS (dPAS) usage in left ventricular (LV) tissues and cardiac fibroblasts from HF patients. CstF64 was upregulated in HF LV tissues and cardiac fibroblasts along with increased deposition of fibrosis genes such as COL1A and FN1 and significant shortening in their 3'UTR. In addition, HF cardiac fibroblasts showed increased transforming growth factor receptor β1 (TGFβR1) expression consistent with significant shortening in 3'UTR of TGFβR1. Upon knockdown of CstF64 from HF fibroblasts, downregulation in pro-fibrotic genes corresponding to lengthening in their 3'UTR was observed. Our finding suggests an important role of CstF64 in myofibroblast activation and promotion of cardiac fibrosis during HF through APA. Therefore, targeting CstF64 mediated RNA processing approach in human HF could provide a new therapeutic treatment strategy for limiting fibrotic remodeling.
    Language English
    Publishing date 2022-01-29
    Publishing country United States
    Document type Journal Article
    ZDB-ID 205723-2
    ISSN 1090-2104 ; 0006-291X ; 0006-291X
    ISSN (online) 1090-2104 ; 0006-291X
    ISSN 0006-291X
    DOI 10.1016/j.bbrc.2022.01.093
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    Zs.A 116: Show issues Location:
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  10. Article ; Online: Lipid nanoparticle-mediated mRNA delivery in lung fibrosis.

    Massaro, Matteo / Wu, Suhong / Baudo, Gherardo / Liu, Haoran / Collum, Scott / Lee, Hyunho / Stigliano, Cinzia / Segura-Ibarra, Victor / Karmouty-Quintana, Harry / Blanco, Elvin

    European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences

    2023  Volume 183, Page(s) 106370

    Abstract: mRNA delivery enables the specific synthesis of proteins with therapeutic potential, representing a powerful strategy in diseases lacking efficacious pharmacotherapies. Idiopathic pulmonary fibrosis (IPF) is a chronic lung disease characterized by ... ...

    Abstract mRNA delivery enables the specific synthesis of proteins with therapeutic potential, representing a powerful strategy in diseases lacking efficacious pharmacotherapies. Idiopathic pulmonary fibrosis (IPF) is a chronic lung disease characterized by excessive extracellular matrix (ECM) deposition and subsequent alveolar remodeling. Alveolar epithelial type 2 cells (AEC2) and fibroblasts represent important targets in IPF given their role in initiating and driving aberrant wound healing responses that lead to excessive ECM deposition. Our objective was to examine a lipid nanoparticle (LNP)-based mRNA construct as a viable strategy to target alveolar epithelial cells and fibroblasts in IPF. mRNA-containing LNPs measuring ∼34 nm had high encapsulation efficiency, protected mRNA from degradation, and exhibited sustained release kinetics. eGFP mRNA LNP transfection in human primary cells proved dose- and time-dependent in vitro. In a bleomycin mouse model of lung fibrosis, luciferase mRNA LNPs administered intratracheally led to site-specific lung accumulation. Importantly, bioluminescence signal was detected in lungs as early as 2 h after delivery, with signal still evident at 48 h. Of note, LNPs were found associated with AEC2 and fibroblasts in vivo. Findings highlight the potential for pulmonary delivery of mRNA in IPF, opening therapeutic avenues aimed at halting and potentially reversing disease progression.
    MeSH term(s) Animals ; Mice ; Humans ; RNA, Messenger/metabolism ; Signal Transduction ; Lung/metabolism ; Idiopathic Pulmonary Fibrosis/metabolism ; Bleomycin ; Fibroblasts/metabolism
    Chemical Substances Lipid Nanoparticles ; RNA, Messenger ; Bleomycin (11056-06-7)
    Language English
    Publishing date 2023-01-13
    Publishing country Netherlands
    Document type Journal Article
    ZDB-ID 1154366-8
    ISSN 1879-0720 ; 0928-0987
    ISSN (online) 1879-0720
    ISSN 0928-0987
    DOI 10.1016/j.ejps.2023.106370
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