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  1. Article ; Online: rhIGF-1 Therapy: A Silver Bullet for Bronchopulmonary Dysplasia Prevention?

    Plosa, Erin J / Benjamin, John T

    American journal of respiratory and critical care medicine

    2020  Volume 201, Issue 9, Page(s) 1032–1033

    MeSH term(s) Bronchopulmonary Dysplasia ; Humans ; Hypertension, Pulmonary ; Infant, Newborn
    Language English
    Publishing date 2020-02-26
    Publishing country United States
    Document type Editorial ; Research Support, N.I.H., Extramural ; Comment
    ZDB-ID 1180953-x
    ISSN 1535-4970 ; 0003-0805 ; 1073-449X
    ISSN (online) 1535-4970
    ISSN 0003-0805 ; 1073-449X
    DOI 10.1164/rccm.202002-0287ED
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  2. Article ; Online: Ahead of their time: hyperoxia injury induces senescence in developing lung fibroblasts.

    Sucre, Jennifer M S / Plosa, Erin J

    American journal of physiology. Lung cellular and molecular physiology

    2019  Volume 317, Issue 5, Page(s) L523–L524

    MeSH term(s) Fibroblasts ; Humans ; Hyperoxia ; Lung
    Language English
    Publishing date 2019-09-11
    Publishing country United States
    Document type Editorial ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Comment
    ZDB-ID 1013184-x
    ISSN 1522-1504 ; 1040-0605
    ISSN (online) 1522-1504
    ISSN 1040-0605
    DOI 10.1152/ajplung.00354.2019
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  3. Article ; Online: Discoidin Domain Receptor 2, a Potential Therapeutic Target in Lung Fibrosis.

    Borza, Corina M / Pozzi, Ambra / Plosa, Erin J

    American journal of respiratory cell and molecular biology

    2018  Volume 59, Issue 3, Page(s) 277–278

    MeSH term(s) Apoptosis ; Discoidin Domain Receptor 2 ; Fibroblasts ; Proto-Oncogene Proteins c-akt ; Signal Transduction
    Chemical Substances Discoidin Domain Receptor 2 (EC 2.7.10.1) ; Proto-Oncogene Proteins c-akt (EC 2.7.11.1)
    Language English
    Publishing date 2018-07-18
    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.2018-0161ED
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  4. Article ; Online: Alveolar repair following LPS-induced injury requires cell-ECM interactions.

    Sucre, Jennifer Ms / Bock, Fabian / Negretti, Nicholas M / Benjamin, John T / Gulleman, Peter M / Dong, Xinyu / Ferguson, Kimberly T / Jetter, Christopher S / Han, Wei / Liu, Yang / Kook, Seunghyi / Gokey, Jason J / Guttentag, Susan H / Kropski, Jonathan A / Blackwell, Timothy S / Zent, Roy / Plosa, Erin J

    JCI insight

    2023  Volume 8, Issue 14

    Abstract: During alveolar repair, alveolar type 2 (AT2) epithelial cell progenitors rapidly proliferate and differentiate into flat AT1 epithelial cells. Failure of normal alveolar repair mechanisms can lead to loss of alveolar structure (emphysema) or development ...

    Abstract During alveolar repair, alveolar type 2 (AT2) epithelial cell progenitors rapidly proliferate and differentiate into flat AT1 epithelial cells. Failure of normal alveolar repair mechanisms can lead to loss of alveolar structure (emphysema) or development of fibrosis, depending on the type and severity of injury. To test if β1-containing integrins are required during repair following acute injury, we administered E. coli lipopolysaccharide (LPS) by intratracheal injection to mice with a postdevelopmental deletion of β1 integrin in AT2 cells. While control mice recovered from LPS injury without structural abnormalities, β1-deficient mice had more severe inflammation and developed emphysema. In addition, recovering alveoli were repopulated with an abundance of rounded epithelial cells coexpressing AT2 epithelial, AT1 epithelial, and mixed intermediate cell state markers, with few mature type 1 cells. AT2 cells deficient in β1 showed persistently increased proliferation after injury, which was blocked by inhibiting NF-κB activation in these cells. Lineage tracing experiments revealed that β1-deficient AT2 cells failed to differentiate into mature AT1 epithelial cells. Together, these findings demonstrate that functional alveolar repair after injury with terminal alveolar epithelial differentiation requires β1-containing integrins.
    MeSH term(s) Mice ; Animals ; Lipopolysaccharides/toxicity ; Escherichia coli ; Lung ; Emphysema ; Integrins
    Chemical Substances Lipopolysaccharides ; Integrins
    Language English
    Publishing date 2023-07-24
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S. ; Research Support, Non-U.S. Gov't
    ISSN 2379-3708
    ISSN (online) 2379-3708
    DOI 10.1172/jci.insight.167211
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Standardization of methods for sampling the distal airspace in mechanically ventilated patients using heat moisture exchange filter fluid.

    Bastarache, Julie A / McNeil, J Brennan / Plosa, Erin J / Sucre, Jennifer S / Kerchberger, V Eric / Habegger, Luke E / Weddle, Elizabeth / Sullivan, Briana / Meegan, Jamie E / Wickersham, Nancy E / Shaver, Ciara M / Ware, Lorraine B

    American journal of physiology. Lung cellular and molecular physiology

    2021  Volume 320, Issue 5, Page(s) L785–L790

    Abstract: Noninvasive sampling of the distal airspace in patients with acute respiratory distress syndrome (ARDS) has long eluded clinical and translational researchers. We recently reported that fluid collected from heat moisture exchange (HME) filters closely ... ...

    Abstract Noninvasive sampling of the distal airspace in patients with acute respiratory distress syndrome (ARDS) has long eluded clinical and translational researchers. We recently reported that fluid collected from heat moisture exchange (HME) filters closely mirrors fluid directly aspirated from the distal airspace. In the current study, we sought to determine fluid yield from different HME types, optimal HME circuit dwell time, and reliability of HME fluid in reflecting the distal airspace. We studied fluid yield from four different filter types by loading increasing volumes of saline and measuring volumes of fluid recovered. We collected filters after 1, 2, and 4 h of dwell time for measurement of fluid volume and total protein from 13 subjects. After identifying 4 h as the optimal dwell time, we measured total protein and IgM in HME fluid from 42 subjects with ARDS and nine with hydrostatic pulmonary edema (HYDRO). We found that the fluid yield varies greatly by filter type. With timed sample collection, fluid recovery increased with increasing circuit dwell time with a median volume of 2.0 mL [interquartile range (IQR) 1.2-2.7] after 4 h. Total protein was higher in the 42 subjects with ARDS compared with nine with HYDRO [median 708 µg/mL (IQR 244-2017) vs. 364 µg/mL (IQR 136-578),
    MeSH term(s) Adult ; Aged ; Aged, 80 and over ; Breath Tests ; Diagnostic Techniques, Respiratory System/standards ; Female ; Hot Temperature ; Humans ; Humidity ; Male ; Middle Aged ; Pulmonary Edema/diagnosis ; Pulmonary Edema/physiopathology ; Respiration, Artificial/methods ; Respiratory Distress Syndrome/diagnosis ; Respiratory Distress Syndrome/physiopathology
    Language English
    Publishing date 2021-03-03
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S.
    ZDB-ID 1013184-x
    ISSN 1522-1504 ; 1040-0605
    ISSN (online) 1522-1504
    ISSN 1040-0605
    DOI 10.1152/ajplung.00595.2020
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  6. Article ; Online: Ligand-independent integrin β1 signaling supports lung adenocarcinoma development.

    Haake, Scott M / Plosa, Erin J / Kropski, Jonathan A / Venton, Lindsay A / Reddy, Anupama / Bock, Fabian / Chang, Betty T / Luna, Allen J / Nabukhotna, Kateryna / Xu, Zhi-Qi / Prather, Rebecca A / Lee, Sharon / Tanjore, Harikrishna / Polosukhin, Vasiliy V / Viquez, Olga M / Jones, Angela / Luo, Wentian / Wilson, Matthew H / Rathmell, W Kimryn /
    Massion, Pierre P / Pozzi, Ambra / Blackwell, Timothy S / Zent, Roy

    JCI insight

    2022  Volume 7, Issue 15

    Abstract: Integrins - the principal extracellular matrix (ECM) receptors of the cell - promote cell adhesion, migration, and proliferation, which are key events for cancer growth and metastasis. To date, most integrin-targeted cancer therapeutics have disrupted ... ...

    Abstract Integrins - the principal extracellular matrix (ECM) receptors of the cell - promote cell adhesion, migration, and proliferation, which are key events for cancer growth and metastasis. To date, most integrin-targeted cancer therapeutics have disrupted integrin-ECM interactions, which are viewed as critical for integrin functions. However, such agents have failed to improve cancer patient outcomes. We show that the highly expressed integrin β1 subunit is required for lung adenocarcinoma development in a carcinogen-induced mouse model. Likewise, human lung adenocarcinoma cell lines with integrin β1 deletion failed to form colonies in soft agar and tumors in mice. Mechanistically, we demonstrate that these effects do not require integrin β1-mediated adhesion to ECM but are dependent on integrin β1 cytoplasmic tail-mediated activation of focal adhesion kinase (FAK). These studies support a critical role for integrin β1 in lung tumorigenesis that is mediated through constitutive, ECM binding-independent signaling involving the cytoplasmic tail.
    MeSH term(s) Adenocarcinoma/genetics ; Adenocarcinoma of Lung/genetics ; Animals ; Humans ; Integrin beta1/genetics ; Integrin beta1/metabolism ; Integrins ; Ligands ; Lung Neoplasms/pathology ; Mice
    Chemical Substances Integrin beta1 ; Integrins ; Ligands
    Language English
    Publishing date 2022-08-08
    Publishing country United States
    Document type Journal Article ; Research Support, U.S. Gov't, Non-P.H.S. ; Research Support, N.I.H., Extramural
    ISSN 2379-3708
    ISSN (online) 2379-3708
    DOI 10.1172/jci.insight.154098
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  7. Article ; Online: Cytomegalovirus infection.

    Plosa, Erin J / Esbenshade, Jennifer C / Fuller, M Paige / Weitkamp, Jörn-Hendrik

    Pediatrics in review

    2012  Volume 33, Issue 4, Page(s) 156–63; quiz 163

    Abstract: Although commonly asymptomatic, congenital CMV infection is the leading cause of nonhereditary SNHL. Other sequelae that may be evident only after the neonatal period can include chorioretinitis, neurodevelopmental delay with mental or motor impairment, ... ...

    Abstract Although commonly asymptomatic, congenital CMV infection is the leading cause of nonhereditary SNHL. Other sequelae that may be evident only after the neonatal period can include chorioretinitis, neurodevelopmental delay with mental or motor impairment, and microcephaly. (13) • Congenital CMV infection is confirmed by detection of the virus in urine, blood, or saliva within the first 3 weeks of life by culture or polymerase chain reaction. A positive test does not necessarily confirm symptomatic CMV disease or need for treatment. (13) • Postnatal CMV infections transmitted through human milk have been reported and may be clinically relevant in extremely premature infants; however, the risk-benefit ratio of pasteurizing human milk for the prevention of postnatal CMV infection is unclear. • Ganciclovir, valganciclovir, foscarnet, cidofovir, and CMV hyperimmune globulin are effective in treating or preventing CMV infections in the immunocompromised host, but require close monitoring for associated toxicities. Treatment for congenital CMV is associated with significant toxicity and uncertain effectiveness. • Based on strong evidence, anticipatory guidance for congenital CMV infection should include hearing tests and neurodevelopmental assessments until school age. (3) In patients with symptomatic congenital CMV infection, lifelong ophthalmologic screening should be included. (4) • Based primarily on consensus, owing to lack of relevant clinical studies, it is not recommended to withhold human milk produced by CMV-seropositive mothers from healthy term infants. (5)(6) • Based on some research evidence, as well as consensus, treatment for congenital CMV is recommended only in symptomatic infants with central nervous system involvement. (9)
    MeSH term(s) Antiviral Agents/therapeutic use ; Child ; Cytomegalovirus Infections/diagnosis ; Cytomegalovirus Infections/epidemiology ; Cytomegalovirus Infections/etiology ; Cytomegalovirus Infections/therapy ; Cytomegalovirus Vaccines ; Global Health ; Humans ; Immunocompromised Host ; Infant ; Infant, Newborn ; Infectious Disease Transmission, Vertical ; Postoperative Complications/diagnosis ; Postoperative Complications/drug therapy ; Transplantation
    Chemical Substances Antiviral Agents ; Cytomegalovirus Vaccines
    Language English
    Publishing date 2012-04
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 774515-1
    ISSN 1526-3347 ; 0191-9601
    ISSN (online) 1526-3347
    ISSN 0191-9601
    DOI 10.1542/pir.33-4-156
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  8. Article ; Online: Nonmuscle myosin II regulation of lung epithelial morphology.

    Plosa, Erin J / Gooding, Kimberly A / Zent, Roy / Prince, Lawrence S

    Developmental dynamics : an official publication of the American Association of Anatomists

    2012  Volume 241, Issue 11, Page(s) 1770–1781

    Abstract: Background: The regulation of epithelial cell shape and orientation during lung branching morphogenesis is not clearly understood. Nonmuscle myosins regulate cell size, morphology, and planar cell polarity. Here, we test the hypothesis that nonmuscle ... ...

    Abstract Background: The regulation of epithelial cell shape and orientation during lung branching morphogenesis is not clearly understood. Nonmuscle myosins regulate cell size, morphology, and planar cell polarity. Here, we test the hypothesis that nonmuscle myosin II (NM II) regulates lung epithelial morphology in a spatially restricted manner.
    Results: Epithelial cell orientation at airway tips in fetal mouse lungs underwent a significant transformation at embryonic day (E) E17. Treatment of E15 lung explants with the NM II inhibitor blebbistatin increased airway branching, epithelial cell size, and the degree of anisotropy in epithelial cells lining the airway stalks. In cultured MLE-12 lung epithelial cells, blebbistatin increased cell velocity, but left the migratory response to FGF-10 unchanged.
    Conclusions: In the developing lung, NM II acts to constrain cell morphology and orientation, but may be suppressed at sites of branching and cell migration. The regulation of epithelial orientation may therefore undergo dynamic variations from E15 to E17.
    MeSH term(s) Animals ; Cell Line ; Cell Movement ; Epithelial Cells/cytology ; Epithelial Cells/metabolism ; Female ; Lung/growth & development ; Lung/metabolism ; Mice ; Myosin Type II/metabolism ; Pregnancy
    Chemical Substances Myosin Type II (EC 3.6.1.-)
    Language English
    Publishing date 2012-09-25
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 1102541-4
    ISSN 1097-0177 ; 1058-8388
    ISSN (online) 1097-0177
    ISSN 1058-8388
    DOI 10.1002/dvdy.23866
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  9. Article ; Online: β1 Integrin regulates adult lung alveolar epithelial cell inflammation.

    Plosa, Erin J / Benjamin, John T / Sucre, Jennifer M / Gulleman, Peter M / Gleaves, Linda A / Han, Wei / Kook, Seunghyi / Polosukhin, Vasiliy V / Haake, Scott M / Guttentag, Susan H / Young, Lisa R / Pozzi, Ambra / Blackwell, Timothy S / Zent, Roy

    JCI insight

    2020  Volume 5, Issue 2

    Abstract: Integrins, the extracellular matrix receptors that facilitate cell adhesion and migration, are necessary for organ morphogenesis; however, their role in maintaining adult tissue homeostasis is poorly understood. To define the functional importance of β1 ... ...

    Abstract Integrins, the extracellular matrix receptors that facilitate cell adhesion and migration, are necessary for organ morphogenesis; however, their role in maintaining adult tissue homeostasis is poorly understood. To define the functional importance of β1 integrin in adult mouse lung, we deleted it after completion of development in type 2 alveolar epithelial cells (AECs). Aged β1 integrin-deficient mice exhibited chronic obstructive pulmonary disease-like (COPD-like) pathology characterized by emphysema, lymphoid aggregates, and increased macrophage infiltration. These histopathological abnormalities were preceded by β1 integrin-deficient AEC dysfunction such as excessive ROS production and upregulation of NF-κB-dependent chemokines, including CCL2. Genetic deletion of the CCL2 receptor, Ccr2, in mice with β1 integrin-deficient type 2 AECs impaired recruitment of monocyte-derived macrophages and resulted in accelerated inflammation and severe premature emphysematous destruction. The lungs exhibited reduced AEC efferocytosis and excessive numbers of inflamed type 2 AECs, demonstrating the requirement for recruited monocytes/macrophages in limiting lung injury and remodeling in the setting of a chronically inflamed epithelium. These studies support a critical role for β1 integrin in alveolar homeostasis in the adult lung.
    MeSH term(s) Aging/metabolism ; Alveolar Epithelial Cells/metabolism ; Alveolar Epithelial Cells/pathology ; Animals ; Cell Adhesion ; Chemokine CCL2/genetics ; Chemokine CCL2/metabolism ; Chemokines/genetics ; Chemokines/metabolism ; Disease Models, Animal ; Epithelium ; Integrin beta1/genetics ; Integrin beta1/metabolism ; Lung/pathology ; Macrophages/metabolism ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Pneumonia/metabolism ; Pneumonia/pathology ; Pulmonary Disease, Chronic Obstructive/metabolism ; Receptors, CCR2/genetics
    Chemical Substances Ccr2 protein, mouse ; Chemokine CCL2 ; Chemokines ; Integrin beta1 ; Itgb1 protein, mouse ; Receptors, CCR2
    Language English
    Publishing date 2020-01-30
    Publishing country United States
    Document type Journal Article
    ISSN 2379-3708
    ISSN (online) 2379-3708
    DOI 10.1172/jci.insight.129259
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  10. Article ; Online: Hyperoxia Injury in the Developing Lung Is Mediated by Mesenchymal Expression of Wnt5A.

    Sucre, Jennifer M S / Vickers, Kasey C / Benjamin, John T / Plosa, Erin J / Jetter, Christopher S / Cutrone, Alissa / Ransom, Meaghan / Anderson, Zachary / Sheng, Quanhu / Fensterheim, Benjamin A / Ambalavanan, Namasivayam / Millis, Bryan / Lee, Ethan / Zijlstra, Andries / Königshoff, Melanie / Blackwell, Timothy S / Guttentag, Susan H

    American journal of respiratory and critical care medicine

    2020  Volume 201, Issue 10, Page(s) 1249–1262

    Abstract: Rationale: ...

    Abstract Rationale:
    MeSH term(s) Alveolar Epithelial Cells/metabolism ; Animals ; Bronchopulmonary Dysplasia ; Coculture Techniques ; Fibroblasts/metabolism ; Gene Expression Profiling ; Gene Expression Regulation, Developmental ; Humans ; Hyperoxia/genetics ; Hyperoxia/metabolism ; In Situ Hybridization ; Lung/growth & development ; Lung/metabolism ; Mesenchymal Stem Cells/drug effects ; Mesenchymal Stem Cells/metabolism ; Mice ; Microscopy, Confocal ; NF-kappa B/antagonists & inhibitors ; Nitriles/pharmacology ; Organ Culture Techniques ; Real-Time Polymerase Chain Reaction ; Sulfones/pharmacology ; Wnt-5a Protein/drug effects ; Wnt-5a Protein/genetics ; Wnt-5a Protein/metabolism
    Chemical Substances 3-(4-methylphenylsulfonyl)-2-propenenitrile ; NF-kappa B ; Nitriles ; Sulfones ; Wnt-5a Protein
    Language English
    Publishing date 2020-02-04
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
    ZDB-ID 1180953-x
    ISSN 1535-4970 ; 0003-0805 ; 1073-449X
    ISSN (online) 1535-4970
    ISSN 0003-0805 ; 1073-449X
    DOI 10.1164/rccm.201908-1513OC
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