Critical role of serum response factor in pulmonary myofibroblast differentiation induced by TGF-beta.

Abstract:

:Transforming growth factor-beta (TGF-beta) is a cytokine implicated in wound healing and in the pathogenesis of pulmonary fibrosis. TGF-beta stimulates myofibroblast differentiation characterized by expression of contractile smooth muscle (SM)-specific proteins such as SM-alpha-actin. In the present study, we examined the role of serum response factor (SRF) in the mechanism of TGF-beta-induced pulmonary myofibroblast differentiation of human lung fibroblasts (HLF). TGF-beta stimulated SM-alpha-actin expression in HLF, which paralleled with a profound induction of SRF expression and activity. Inhibition of SRF by the pharmacologic SRF inhibitor (CCG-1423), or via adenovirus-mediated transduction of SRF short hairpin RNA (shSRF), blocked the expression of both SRF and SM-alpha-actin in response to TGF-beta without affecting Smad-mediated signaling of TGF-beta. However, forced expression of SRF on its own did not promote SM-alpha-actin expression, whereas expression of the constitutively transactivated SRF fusion protein (SRF-VP16) was sufficient to induce SM-alpha-actin expression, suggesting that both expression and transactivation of SRF are important. Activation of protein kinase A (PKA) by forskolin or iloprost resulted in a significant inhibition of SM-alpha-actin expression induced by TGF-beta, and this was associated with inhibition of both SRF expression and activity, but not of Smad-mediated gene transcription. In summary, this is the first direct demonstration that TGF-beta-induced pulmonary myofibroblast differentiation is mediated by SRF, and that inhibition of myofibroblast differentiation by PKA occurs through down-regulation of SRF expression levels and SRF activity, independent of Smad signaling.

authors

Sandbo N,Kregel S,Taurin S,Bhorade S,Dulin NO

doi

10.1165/rcmb.2008-0288OC

subject

Has Abstract

pub_date

2009-09-01 00:00:00

pages

332-8

issue

3

eissn

1044-1549

issn

1535-4989

pii

2008-0288OC

journal_volume

41

pub_type

杂志文章
  • Reversible or irreversible remodeling in pulmonary arterial hypertension.

    abstract::Vascular remodeling is an important pathological feature of pulmonary arterial hypertension (PAH), which leads to increased pulmonary vascular resistance, with marked proliferation of pulmonary artery smooth muscle cells (SMC) and/or endothelial cells (EC). Successful treatment of experimental PAH with a platelet-deri...

    journal_title:American journal of respiratory cell and molecular biology

    pub_type: 杂志文章,评审

    doi:10.1165/rcmb.2009-0389TR

    authors: Sakao S,Tatsumi K,Voelkel NF

    更新日期:2010-12-01 00:00:00

  • Inhalation of Stachybotrys chartarum Fragments Induces Pulmonary Arterial Remodeling.

    abstract::Stachybotrys chartarum is a fungal contaminant within the built environment and a respiratory health concern in the United States. The objective of this study was to characterize the mechanisms influencing pulmonary immune responses to repeatedly inhaled S. chartarum. Groups of B6C3F1/N mice repeatedly inhaled viable ...

    journal_title:American journal of respiratory cell and molecular biology

    pub_type: 杂志文章

    doi:10.1165/rcmb.2019-0221OC

    authors: Croston TL,Lemons AR,Barnes MA,Goldsmith WT,Orandle MS,Nayak AP,Germolec DR,Green BJ,Beezhold DH

    更新日期:2020-05-01 00:00:00

  • Corticosteroids inhibit sphingosine 1-phosphate-induced interleukin-6 secretion from human airway smooth muscle via mitogen-activated protein kinase phosphatase 1-mediated repression of mitogen and stress-activated protein kinase 1.

    abstract::Sphingosine 1-phosphate (S1P) is a bioactive sphingolipid that plays an important proinflammatory role in asthmatic airways. Corticosteroids are first-line antiinflammatories in asthma; however, their repressive effects on S1P-induced cytokine secretion have not been investigated. To address this, our in vitro study r...

    journal_title:American journal of respiratory cell and molecular biology

    pub_type: 杂志文章

    doi:10.1165/rcmb.2013-0208OC

    authors: Che W,Parmentier J,Seidel P,Manetsch M,Ramsay EE,Alkhouri H,Ge Q,Armour CL,Ammit AJ

    更新日期:2014-02-01 00:00:00

  • The matrix metalloproteinases and their inhibitors.

    abstract::A number of metalloproteinases that degrade the extracellular matrix of connective tissues and two specific tissue inhibitors of metalloproteinases (TIMPs) have now been isolated, characterized, and cloned. Comparison of the enzyme sequences has allowed the delineation of domain structures, and initial studies have be...

    journal_title:American journal of respiratory cell and molecular biology

    pub_type: 杂志文章,评审

    doi:10.1165/ajrcmb/7.2.120

    authors: Murphy G,Docherty AJ

    更新日期:1992-08-01 00:00:00

  • Endothelin-1 induces a glycolytic switch in pulmonary arterial endothelial cells via the mitochondrial translocation of endothelial nitric oxide synthase.

    abstract::Recent studies have indicated that, during the development of pulmonary hypertension (PH), there is a switch from oxidative phosphorylation to glycolysis in the pulmonary endothelium. However, the mechanisms underlying this phenomenon have not been elucidated. Endothelin (ET)-1, an endothelial-derived vasoconstrictor ...

    journal_title:American journal of respiratory cell and molecular biology

    pub_type: 杂志文章

    doi:10.1165/rcmb.2013-0187OC

    authors: Sun X,Kumar S,Sharma S,Aggarwal S,Lu Q,Gross C,Rafikova O,Lee SG,Dasarathy S,Hou Y,Meadows ML,Han W,Su Y,Fineman JR,Black SM

    更新日期:2014-06-01 00:00:00

  • Cigarette smoke stimulates matrix metalloproteinase-2 activity via EGR-1 in human lung fibroblasts.

    abstract::Cigarette smoking is a major risk factor for chronic obstructive pulmonary disease (COPD). Recent reports of increased matrix metalloproteinase-2 (MMP-2) in lungs of patients with emphysema support the paradigm of proteinase/antiproteinase imbalance in the pathogenesis of COPD. We sought to define the signaling pathwa...

    journal_title:American journal of respiratory cell and molecular biology

    pub_type: 杂志文章

    doi:10.1165/rcmb.2006-0106OC

    authors: Ning W,Dong Y,Sun J,Li C,Matthay MA,Feghali-Bostwick CA,Choi AM

    更新日期:2007-04-01 00:00:00

  • Post-infection A77-1726 blocks pathophysiologic sequelae of respiratory syncytial virus infection.

    abstract::Despite respiratory syncytial virus (RSV) bronchiolitis remaining the most common cause of lower respiratory tract disease in infants worldwide, treatment has progressed little in the past 30 years. The aim of our study was to determine whether post-infection administration of de novo pyrimidine synthesis inhibitors c...

    journal_title:American journal of respiratory cell and molecular biology

    pub_type: 杂志文章

    doi:10.1165/rcmb.2007-0142OC

    authors: Davis IC,Lazarowski ER,Chen FP,Hickman-Davis JM,Sullender WM,Matalon S

    更新日期:2007-10-01 00:00:00

  • Sustained adenosine exposure causes lung endothelial barrier dysfunction via nucleoside transporter-mediated signaling.

    abstract::Previous studies by our group as well as others have shown that acute adenosine exposure enhances lung vascular endothelial barrier integrity and protects against increased permeability lung edema. In contrast, there is growing evidence that sustained adenosine exposure has detrimental effects on the lungs, including ...

    journal_title:American journal of respiratory cell and molecular biology

    pub_type: 杂志文章

    doi:10.1165/rcmb.2012-0012OC

    authors: Lu Q,Newton J,Hsiao V,Shamirian P,Blackburn MR,Pedroza M

    更新日期:2012-11-01 00:00:00

  • TOLL-interacting Protein in Pulmonary Diseases: Abiding by the Goldilocks Principle.

    abstract::Toll-interacting protein (TOLLIP) is an intracellular adaptor protein with diverse actions throughout the body. In a context- and cell type-specific manner, TOLLIP can function as an inhibitor of inflammation and endoplasmic reticulum stress, an activator of autophagy, or a critical regulator of intracellular vacuole ...

    journal_title:American journal of respiratory cell and molecular biology

    pub_type: 杂志文章

    doi:10.1165/rcmb.2020-0470TR

    authors: Li X,Goobie GC,Gregory AD,Kass DJ,Zhang Y

    更新日期:2020-11-24 00:00:00

  • Clarithromycin inhibits interleukin-13-induced goblet cell hyperplasia in human airway cells.

    abstract::IL-13 is a T-helper class 2 cytokine that induces goblet cell hyperplasia and mucus production in airway epithelial cells. Because macrolide antibiotics are known to have immunomodulatory and mucoregulatory properties, the aim of this study was to examine the effect of clarithromycin on IL-13-induced goblet cell hyper...

    journal_title:American journal of respiratory cell and molecular biology

    pub_type: 杂志文章

    doi:10.1165/rcmb.2010-0327OC

    authors: Tanabe T,Kanoh S,Tsushima K,Yamazaki Y,Kubo K,Rubin BK

    更新日期:2011-11-01 00:00:00

  • Contribution of upregulated airway endothelin-1 expression to airway smooth muscle and epithelial cell DNA synthesis after repeated allergen exposure of sensitized Brown-Norway rats.

    abstract::Endothelin-1 is a potent bronchoconstrictor peptide with pro-inflammatory and growth-promoting properties. After exposure of sensitized Brown-Norway rats to six repeated ovalbumin exposures, there was an increase in pro-endothelin (ET)-1 messenger RNA compared with saline-exposed control rats 24 h after the final expo...

    journal_title:American journal of respiratory cell and molecular biology

    pub_type: 杂志文章

    doi:10.1165/ajrcmb.23.5.3909

    authors: Salmon M,Liu YC,Mak JC,Rousell J,Huang TJ,Hisada T,Nicklin PL,Chung KF

    更新日期:2000-11-01 00:00:00

  • Quantitative trait loci controlling allergen-induced airway hyperresponsiveness in inbred mice.

    abstract::Identification of the genetic loci underlying asthma in humans has been hampered by variability in clinical phenotype, uncontrolled environmental influences, and genetic heterogeneity. To circumvent these complications, the genetic regulation of asthma-associated phenotypes was studied in a murine model. We characteri...

    journal_title:American journal of respiratory cell and molecular biology

    pub_type: 杂志文章

    doi:10.1165/ajrcmb.23.4.4199

    authors: Ewart SL,Kuperman D,Schadt E,Tankersley C,Grupe A,Shubitowski DM,Peltz G,Wills-Karp M

    更新日期:2000-10-01 00:00:00

  • Characterization of lung hyperresponsiveness, inflammation, and alveolar macrophage mediator production in allergy resistant and susceptible rats.

    abstract::To better understand asthma pathogenesis, we characterized airway responsiveness, lung inflammation, and mediator production of alveolar macrophages (AM) after allergen sensitization and challenge in two strains of rats showing different susceptibilities in developing airway allergic reactions. Airway responsiveness t...

    journal_title:American journal of respiratory cell and molecular biology

    pub_type: 杂志文章

    doi:10.1165/ajrcmb.26.5.4737

    authors: Careau E,Sirois J,Bissonnette EY

    更新日期:2002-05-01 00:00:00

  • Hyperoxia alone causes changes in lung proteoglycans and hyaluronan in neonatal rat pups.

    abstract::Specific changes in composition and content of lung extracellular matrix (ECM) proteoglycans (PGs) and hyaluronan (HA) have been observed during the acute response to damage in several forms of injury including infant respiratory distress syndrome (IRDS). These ECM components are thought to modulate the healing respon...

    journal_title:American journal of respiratory cell and molecular biology

    pub_type: 杂志文章

    doi:10.1165/ajrcmb.13.6.7576700

    authors: Juul SE,Krueger RC Jr,Scofield L,Hershenson MB,Schwartz NB

    更新日期:1995-12-01 00:00:00

  • Upregulation of neuropeptides and neuropeptide receptors in a murine model of immune inflammation in lung parenchyma.

    abstract::The lung is richly supplied with peptidergic nerves that store and secrete substance P (SP), vasoactive intestinal peptide (VIP), and other neuropeptides known to potently modulate leukocyte function in vitro and airway inflammation in vivo. To investigate and characterize neuromodulation of immune responses compartme...

    journal_title:American journal of respiratory cell and molecular biology

    pub_type: 杂志文章

    doi:10.1165/ajrcmb.16.2.9032120

    authors: Kaltreider HB,Ichikawa S,Byrd PK,Ingram DA,Kishiyama JL,Sreedharan SP,Warnock ML,Beck JM,Goetzl EJ

    更新日期:1997-02-01 00:00:00

  • ST depression, arrhythmia, vagal dominance, and reduced cardiac micro-RNA in particulate-exposed rats.

    abstract::Recently, investigators demonstrated associations between fine particulate matter (PM)-associated metals and adverse health effects. Residual oil fly ash (ROFA), a waste product of fossil fuel combustion from boilers, is rich in the transition metals Fe, Ni, and V, and when released as a fugitive particle, is an impor...

    journal_title:American journal of respiratory cell and molecular biology

    pub_type: 杂志文章

    doi:10.1165/rcmb.2009-0456OC

    authors: Farraj AK,Hazari MS,Haykal-Coates N,Lamb C,Winsett DW,Ge Y,Ledbetter AD,Carll AP,Bruno M,Ghio A,Costa DL

    更新日期:2011-02-01 00:00:00

  • Pseudomonas aeruginosa induction of apoptosis in respiratory epithelial cells: analysis of the effects of cystic fibrosis transmembrane conductance regulator dysfunction and bacterial virulence factors.

    abstract::Airway epithelial cells can respond to infection by activating several signaling pathways. We examined the induction of apoptosis in response to Pseudomonas aeruginosa PAO1 in normal cells and several cystic fibrosis (CF) and corrected cell lines. Epithelial cells in monolayers with tight junctions, confirmed by apica...

    journal_title:American journal of respiratory cell and molecular biology

    pub_type: 杂志文章

    doi:10.1165/ajrcmb.23.3.4098

    authors: Rajan S,Cacalano G,Bryan R,Ratner AJ,Sontich CU,van Heerckeren A,Davis P,Prince A

    更新日期:2000-09-01 00:00:00

  • Modified High-Molecular-Weight Hyaluronan Promotes Allergen-Specific Immune Tolerance.

    abstract::The extracellular matrix in asthmatic lungs contains abundant low-molecular-weight hyaluronan, and this is known to promote antigen presentation and allergic responses. Conversely, high-molecular-weight hyaluronan (HMW-HA), typical of uninflamed tissues, is known to suppress inflammation. We investigated whether HMW-H...

    journal_title:American journal of respiratory cell and molecular biology

    pub_type: 杂志文章

    doi:10.1165/rcmb.2016-0111OC

    authors: Gebe JA,Yadava K,Ruppert SM,Marshall P,Hill P,Falk BA,Sweere JM,Han H,Kaber G,Harten IA,Medina C,Mikecz K,Ziegler SF,Balaji S,Keswani SG,Perez VA,Butte MJ,Nadeau K,Altemeier WA,Fanger N,Bollyky PL

    更新日期:2017-01-01 00:00:00

  • Differential regulation of the genes encoding platelet-derived growth factor receptor and its ligand in rat lung during microvascular and alveolar wall remodeling in hyperoxia.

    abstract::The growth factors that operate while the lung remodels in hyperoxia are not known. At the lung periphery, high oxygen levels cause cell hypertrophy and hyperplasia, and this results in a thickening of the alveolar-capillary membrane and the walls of its associated microvessels. The present study examines gene express...

    journal_title:American journal of respiratory cell and molecular biology

    pub_type: 杂志文章

    doi:10.1165/ajrcmb/7.3.278

    authors: Powell PP,Wang CC,Jones R

    更新日期:1992-09-01 00:00:00

  • Functional, morphological, and phenotypical differences between rat alveolar and interstitial macrophages.

    abstract::Alveolar macrophages (AM) and interstitial macrophages (IM) from rat lungs were characterized with respect to morphology, phagocytosis, adhesion properties, and phenotype. AM were recovered by lung lavage and IM by treatment of the lung tissue with DNAse and collagenase. The AM were enzyme treated in the same way as t...

    journal_title:American journal of respiratory cell and molecular biology

    pub_type: 杂志文章

    doi:10.1165/ajrcmb.16.5.9160840

    authors: Johansson A,Lundborg M,Sköld CM,Lundahl J,Tornling G,Eklund A,Camner P

    更新日期:1997-05-01 00:00:00

  • Surfactant protein A differentially regulates IFN-gamma- and LPS-induced nitrite production by rat alveolar macrophages.

    abstract::Although several studies have demonstrated that the pulmonary collectins surfactant protein (SP)-A and SP-D contribute to innate immunity by enhancing pathogen phagocytosis, the role of SP-A and SP-D in regulating production of free radicals and cytokines is controversial. We hypothesized that the state and mechanism ...

    journal_title:American journal of respiratory cell and molecular biology

    pub_type: 杂志文章

    doi:10.1165/ajrcmb.23.6.4083

    authors: Stamme C,Walsh E,Wright JR

    更新日期:2000-12-01 00:00:00

  • Rhinovirus-induced IL-1β release from bronchial epithelial cells is independent of functional P2X7.

    abstract::Airway epithelial cell defenses to viral infections are often compromised in disease or injury. Danger molecules, including ATP, are released during infection and contribute to nucleotide receptor-dependent inflammatory responses, largely through P2X(7). Although respiratory epithelium has been shown to express a vari...

    journal_title:American journal of respiratory cell and molecular biology

    pub_type: 杂志文章

    doi:10.1165/rcmb.2011-0267OC

    authors: Shi L,Manthei DM,Guadarrama AG,Lenertz LY,Denlinger LC

    更新日期:2012-09-01 00:00:00

  • Glucose Transporter 1-Dependent Glycolysis Is Increased during Aging-Related Lung Fibrosis, and Phloretin Inhibits Lung Fibrosis.

    abstract::Aging is associated with metabolic diseases such as type 2 diabetes mellitus, cardiovascular disease, cancer, and neurodegeneration. Aging contributes to common processes including metabolic dysfunction, DNA damage, and reactive oxygen species generation. Although glycolysis has been linked to cell growth and prolifer...

    journal_title:American journal of respiratory cell and molecular biology

    pub_type: 杂志文章

    doi:10.1165/rcmb.2016-0225OC

    authors: Cho SJ,Moon JS,Lee CM,Choi AM,Stout-Delgado HW

    更新日期:2017-04-01 00:00:00

  • Alveolar macrophage-particle relationships during lung clearance.

    abstract::Retention kinetics for insoluble particles that deposit in the lung oftentimes resemble a multicomponent process during alveolar clearance, with each component appearing to follow simple first-order kinetics. Inasmuch as alveolar macrophages (AM) are thought to play an important role in particle removal from the lung,...

    journal_title:American journal of respiratory cell and molecular biology

    pub_type: 杂志文章

    doi:10.1165/ajrcmb/1.2.145

    authors: Lehnert BE,Valdez YE,Tietjen GL

    更新日期:1989-08-01 00:00:00

  • Serum accelerates the loss of type II cell differentiation in vitro.

    abstract::The differentiated phenotype of the alveolar type II cell is rapidly altered in vitro. To evaluate factors that might influence this process, we isolated and plated rat type II cells in serum-supplemented media to promote adherence and then maintained the cells in a simple nutrient medium in the absence (S- cells) or ...

    journal_title:American journal of respiratory cell and molecular biology

    pub_type: 杂志文章

    doi:10.1165/ajrcmb/3.4.311

    authors: Paine R 3rd,Joyce-Brady M,Clement A,Brody JS

    更新日期:1990-10-01 00:00:00

  • Human alveolar macrophages inhibit receptor-mediated increases in intracellular calcium concentration in lymphocytes.

    abstract::Prior studies have demonstrated that human alveolar macrophages (AM) are suppressive of lymphocyte function, through the mechanism of inhibition is unclear. In the current study, human AM inhibited receptor-mediated increases in intracellular calcium concentration ([Ca2+]i) in T cells, natural killer cells, and B cell...

    journal_title:American journal of respiratory cell and molecular biology

    pub_type: 杂志文章

    doi:10.1165/ajrcmb/5.5.411

    authors: Yarbrough WC Jr,Wilkes DS,Weissler JC

    更新日期:1991-11-01 00:00:00

  • Autocrine ligands for the epidermal growth factor receptor mediate interleukin-8 release from bronchial epithelial cells in response to cigarette smoke.

    abstract::Airway neutrophilia is a prominent feature of chronic obstructive pulmonary disease. As cigarette smoke (CS) and epidermal growth factor (EGF) both cause release of interleukin-8 (IL-8) from epithelial cells in vitro, we investigated whether autocrine ligands for the EGF receptor (EGFR) are involved in this proinflamm...

    journal_title:American journal of respiratory cell and molecular biology

    pub_type: 杂志文章

    doi:10.1165/ajrcmb.27.1.4789

    authors: Richter A,O'Donnell RA,Powell RM,Sanders MW,Holgate ST,Djukanović R,Davies DE

    更新日期:2002-07-01 00:00:00

  • Genetic Variation along the Histamine Pathway in Children with Allergic versus Nonallergic Asthma.

    abstract::Histamine is an important mediator in the pathogenesis of asthma. Variation in genes along the histamine production, response, and degradation pathway may be important in predicting response to antihistamines. We hypothesize that differences exist among single-nucleotide polymorphisms (SNPs) in genes of the histamine ...

    journal_title:American journal of respiratory cell and molecular biology

    pub_type: 杂志文章

    doi:10.1165/rcmb.2014-0493OC

    authors: Anvari S,Vyhlidal CA,Dai H,Jones BL

    更新日期:2015-12-01 00:00:00

  • Alpha,beta-unsaturated aldehydes in cigarette smoke release inflammatory mediators from human macrophages.

    abstract::Smoking cigarettes is the major risk factor for chronic obstructive pulmonary disease (COPD). COPD is a condition associated with chronic pulmonary inflammation, characterized by macrophage activation, neutrophil recruitment, and cell injury. Many substances contained in cigarette smoke, including reactive oxygen spec...

    journal_title:American journal of respiratory cell and molecular biology

    pub_type: 杂志文章

    doi:10.1165/rcmb.2007-0130OC

    authors: Facchinetti F,Amadei F,Geppetti P,Tarantini F,Di Serio C,Dragotto A,Gigli PM,Catinella S,Civelli M,Patacchini R

    更新日期:2007-11-01 00:00:00

  • Aging enhances susceptibility to cigarette smoke-induced inflammation through bronchiolar chemokines.

    abstract::Cigarette smoking and aging are major risk factors for chronic obstructive pulmonary disease. An unsolved question is whether elderly lungs are particularly vulnerable to cigarette smoke (CS) exposure. In this study, we used a mouse model to test the hypothesis that aging increases the susceptibility to CS-induced pul...

    journal_title:American journal of respiratory cell and molecular biology

    pub_type: 杂志文章

    doi:10.1165/rcmb.2009-0025OC

    authors: Moriyama C,Betsuyaku T,Ito Y,Hamamura I,Hata J,Takahashi H,Nasuhara Y,Nishimura M

    更新日期:2010-03-01 00:00:00