LIVIVO - The Search Portal for Life Sciences

zur deutschen Oberfläche wechseln
Advanced search

Search results

Result 1 - 6 of total 6

Search options

  1. Article ; Online: Epithelial Yap/Taz are required for functional alveolar regeneration following acute lung injury

    Gianluca T. DiGiovanni / Wei Han / Taylor P. Sherrill / Chase J. Taylor / David S. Nichols / Natalie M. Geis / Ujjal K. Singha / Carla L. Calvi / A. Scott McCall / Molly M. Dixon / Yang Liu / Ji-Hoon Jang / Sergey S. Gutor / Vasiliy V. Polosukhin / Timothy S. Blackwell / Jonathan A. Kropski / Jason J. Gokey

    JCI Insight, Vol 8, Iss

    2023  Volume 19

    Abstract: A hallmark of idiopathic pulmonary fibrosis (IPF) and other interstitial lung diseases is dysregulated repair of the alveolar epithelium. The Hippo pathway effector transcription factors YAP and TAZ are implicated as essential for type 1 and type 2 ... ...

    Abstract A hallmark of idiopathic pulmonary fibrosis (IPF) and other interstitial lung diseases is dysregulated repair of the alveolar epithelium. The Hippo pathway effector transcription factors YAP and TAZ are implicated as essential for type 1 and type 2 alveolar epithelial cell (AT1 and AT2) differentiation in the developing lung, yet aberrant activation of YAP/TAZ is a prominent feature of the dysregulated alveolar epithelium in IPF. In these studies, we sought to define the functional role of YAP/TAZ activity during alveolar regeneration. We demonstrated that Yap and Taz were normally activated in AT2 cells shortly after injury, and deletion of Yap/Taz in AT2 cells led to pathologic alveolar remodeling, failure of AT2-to-AT1 cell differentiation, increased collagen deposition, exaggerated neutrophilic inflammation, and increased mortality following injury induced by a single dose of bleomycin. Loss of Yap/Taz activity prior to an LPS injury prevented AT1 cell regeneration, led to intraalveolar collagen deposition, and resulted in persistent innate inflammation. These findings establish that AT2 cell Yap/Taz activity is essential for functional alveolar epithelial repair and prevention of fibrotic remodeling.
    Keywords Pulmonology ; Medicine ; R
    Subject code 610
    Language English
    Publishing date 2023-10-01T00:00:00Z
    Publisher American Society for Clinical investigation
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

    Full text online

    More links

    Kategorien

    Inter-library loan at ZB MED

    Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

  2. Article ; Online: Androgen receptor signaling promotes Treg suppressive function during allergic airway inflammation

    Vivek D. Gandhi / Jacqueline-Yvonne Cephus / Allison E. Norlander / Nowrin U. Chowdhury / Jian Zhang / Zachary J. Ceneviva / Elie Tannous / Vasiliy V. Polosukhin / Nathan D. Putz / Nancy Wickersham / Amrit Singh / Lorraine B. Ware / Julie A. Bastarache / Ciara M. Shaver / Hong Wei Chu / R. Stokes Peebles Jr. / Dawn C. Newcomb

    The Journal of Clinical Investigation, Vol 132, Iss

    2022  Volume 4

    Abstract: Women have higher prevalence of asthma compared with men. In asthma, allergic airway inflammation is initiated by IL-33 signaling through ST2, leading to increased IL-4, IL-5, and IL-13 production and eosinophil infiltration. Foxp3+ Tregs suppress and ... ...

    Abstract Women have higher prevalence of asthma compared with men. In asthma, allergic airway inflammation is initiated by IL-33 signaling through ST2, leading to increased IL-4, IL-5, and IL-13 production and eosinophil infiltration. Foxp3+ Tregs suppress and ST2+ Tregs promote allergic airway inflammation. Clinical studies showed that the androgen dehydroepiandrosterone (DHEA) reduced asthma symptoms in patients, and mouse studies showed that androgen receptor (AR) signaling decreased allergic airway inflammation. Yet the impact of AR signaling on lung Tregs remains unclear. Using AR-deficient and Foxp3 fate-mapping mice, we determined that AR signaling increased Treg suppression during Alternaria extract (Alt Ext; allergen) challenge by stabilizing Foxp3+ Tregs and limiting the number of ST2+ ex-Tregs and IL-13+ Th2 cells and ex-Tregs. AR signaling also decreased Alt Ext–induced ST2+ Tregs in mice by limiting expression of Gata2, a transcription factor for ST2, and by decreasing Alt Ext–induced IL-33 production from murine airway epithelial cells. We confirmed our findings in human cells where 5α-dihydrotestosterone (DHT), an androgen, decreased IL-33–induced ST2 expression in lung Tregs and decreased Alt Ext–induced IL-33 secretion in human bronchial epithelial cells. Our findings showed that AR signaling stabilized Treg suppressive function, providing a mechanism for the sex difference in asthma.
    Keywords Inflammation ; Pulmonology ; Medicine ; R
    Subject code 610
    Language English
    Publishing date 2022-02-01T00:00:00Z
    Publisher American Society for Clinical Investigation
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

    Full text online

    More links

    Kategorien

    Inter-library loan at ZB MED

    Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

  3. Article ; Online: p52 expression enhances lung cancer progression

    Jamie A. Saxon / Hui Yu / Vasiliy V. Polosukhin / Georgios T. Stathopoulos / Linda A. Gleaves / Allyson G. McLoed / Pierre P. Massion / Fiona E. Yull / Zhongming Zhao / Timothy S. Blackwell

    Scientific Reports, Vol 8, Iss 1, Pp 1-

    2018  Volume 12

    Abstract: Abstract While many studies have demonstrated that canonical NF-κB signaling is a central pathway in lung tumorigenesis, the role of non-canonical NF-κB signaling in lung cancer remains undefined. We observed frequent nuclear accumulation of the non- ... ...

    Abstract Abstract While many studies have demonstrated that canonical NF-κB signaling is a central pathway in lung tumorigenesis, the role of non-canonical NF-κB signaling in lung cancer remains undefined. We observed frequent nuclear accumulation of the non-canonical NF-κB component p100/p52 in human lung adenocarcinoma. To investigate the impact of non-canonical NF-κB signaling on lung carcinogenesis, we employed transgenic mice with doxycycline-inducible expression of p52 in airway epithelial cells. p52 over-expression led to increased tumor number and progression after injection of the carcinogen urethane. Gene expression analysis of lungs from transgenic mice combined with in vitro studies suggested that p52 promotes proliferation of lung epithelial cells through regulation of cell cycle-associated genes. Using gene expression and patient information from The Cancer Genome Atlas (TCGA) database, we found that expression of p52-associated genes was increased in lung adenocarcinomas and correlated with reduced survival, even in early stage disease. Analysis of p52-associated gene expression in additional human lung adenocarcinoma datasets corroborated these findings. Together, these studies implicate the non-canonical NF-κB component p52 in lung carcinogenesis and suggest modulation of p52 activity and/or downstream mediators as new therapeutic targets.
    Keywords Medicine ; R ; Science ; Q
    Subject code 570
    Language English
    Publishing date 2018-04-01T00:00:00Z
    Publisher Nature Publishing Group
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

    Full text online

    More links

    Kategorien

    Inter-library loan at ZB MED

    Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

  4. Article ; Online: Ligand-independent integrin β1 signaling supports lung adenocarcinoma development

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

    JCI Insight, Vol 7, Iss

    2022  Volume 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.
    Keywords Oncology ; Medicine ; R
    Subject code 571
    Language English
    Publishing date 2022-08-01T00:00:00Z
    Publisher American Society for Clinical investigation
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

    Full text online

    More links

    Kategorien

    Inter-library loan at ZB MED

    Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

  5. Article ; Online: Airway bacteria drive a progressive COPD-like phenotype in mice with polymeric immunoglobulin receptor deficiency

    Bradley W. Richmond / Robert M. Brucker / Wei Han / Rui-Hong Du / Yongqin Zhang / Dong-Sheng Cheng / Linda Gleaves / Rasul Abdolrasulnia / Dina Polosukhina / Peter E. Clark / Seth R. Bordenstein / Timothy S. Blackwell / Vasiliy V. Polosukhin

    Nature Communications, Vol 7, Iss 1, Pp 1-

    2016  Volume 12

    Abstract: The mechanisms driving lung inflammation and remodelling in chronic obstructive pulmonary disease (COPD) are incompletely understood. Here the authors show that lack of secretory IgA promotes bacterial invasion in small airways, resulting in leukocyte ... ...

    Abstract The mechanisms driving lung inflammation and remodelling in chronic obstructive pulmonary disease (COPD) are incompletely understood. Here the authors show that lack of secretory IgA promotes bacterial invasion in small airways, resulting in leukocyte recruitment and a COPD-like phenotype.
    Keywords Science ; Q
    Language English
    Publishing date 2016-04-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

    Full text online

    More links

    Kategorien

    Inter-library loan at ZB MED

    Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

  6. Article ; Online: Neutrophil-Derived IL-1β Impairs the Efficacy of NF-κB Inhibitors against Lung Cancer

    Allyson G. McLoed / Taylor P. Sherrill / Dong-Sheng Cheng / Wei Han / Jamie A. Saxon / Linda A. Gleaves / Pingsheng Wu / Vasiliy V. Polosukhin / Michael Karin / Fiona E. Yull / Georgios T. Stathopoulos / Vassilis Georgoulias / Rinat Zaynagetdinov / Timothy S. Blackwell

    Cell Reports, Vol 16, Iss 1, Pp 120-

    2016  Volume 132

    Abstract: Although epithelial NF-κB signaling is important for lung carcinogenesis, NF-κB inhibitors are ineffective for cancer treatment. To explain this paradox, we studied mice with genetic deletion of IKKβ in myeloid cells and found enhanced tumorigenesis in ... ...

    Abstract Although epithelial NF-κB signaling is important for lung carcinogenesis, NF-κB inhibitors are ineffective for cancer treatment. To explain this paradox, we studied mice with genetic deletion of IKKβ in myeloid cells and found enhanced tumorigenesis in KrasG12D and urethane models of lung cancer. Myeloid-specific inhibition of NF-κB augmented pro-IL-1β processing by cathepsin G in neutrophils, leading to increased IL-1β and enhanced epithelial cell proliferation. Combined treatment with bortezomib, a proteasome inhibitor that blocks NF-κB activation, and IL-1 receptor antagonist reduced tumor formation and growth in vivo. In lung cancer patients, plasma IL-1β levels correlated with poor prognosis, and IL-1β increased following bortezomib treatment. Together, our studies elucidate an important role for neutrophils and IL-1β in lung carcinogenesis and resistance to NF-κB inhibitors.
    Keywords Biology (General) ; QH301-705.5
    Subject code 610
    Language English
    Publishing date 2016-06-01T00:00:00Z
    Publisher Elsevier
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

    Full text online

    More links

    Kategorien

    Inter-library loan at ZB MED

    Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

To top