Susanne Herold

Vitos Gießen-Marburg, Giessen, Hesse, Germany

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Publications (65)268.84 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: The gasotransmitter hydrogen sulfide (H2S) is emerging as a mediator of lung physiology and disease. Recent studies revealed that H2S administration limited perturbations to lung structure in experimental animal models of bronchopulmonary dysplasia (BPD), partially restoring alveolarization, limiting pulmonary hypertension, limiting inflammation, and promoting epithelial repair. No studies have addressed roles for endogenous H2S in lung development. H2S is endogenously generated by cystathionine β-synthase (Cbs) and cystathionine γ-lyase (Cth). We demonstrate here that the expression of Cbs and Cth in mouse lungs is dynamically regulated during lung alveolarization, and that alveolarization is blunted in Cbs(-/-) and Cth(-/-) mouse pups, where a 50% reduction in the total number of alveoli was observed, without any impact on septal thickness. Laser-capture microdissection and immunofluorescence staining indicated that Cbs and Cth were expressed in the airway epithelium and lung vessels. Loss of Cbs and Cth led to a 100-500% increase in the muscularization of small- and medium-sized lung vessels, which was accompanied by increased vessel wall thickness, and an apparent decrease in lung vascular supply. Ablation of Cbs expression using small interfering RNA, or pharmacological inhibition of Cth using propargylglycine in lung endothelial cells limited angiogenic capacity, causing a 30-40% decrease in tube length, and a 50% decrease in number of tubes formed. In contrast, exogenous administration of H2S with GYY4137 promoted endothelial tube formation. These data confirm a key role for the H2S generating enzymes Cbs and Cth in pulmonary vascular development and homeostasis, and lung alveolarization. Copyright © 2015, American Journal of Physiology - Lung Cellular and Molecular Physiology.
    AJP Lung Cellular and Molecular Physiology 07/2015; DOI:10.1152/ajplung.00134.2015 · 4.04 Impact Factor
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    ABSTRACT: Acute respiratory distress syndrome (ARDS) represents a major cause of mortality in intensive care patients. Activation of peroxisome proliferator-activated receptor-α (PPAR-α) by fibrates, such as WY-14643 (WY), has been described to beneficially influence inflammation and experimental lung injury. The impact of PPAR-α activation on alveolar epithelial cells (AEC) has not been studied yet. To investigate the effect of PPAR-α activator WY in wild-type (WT) and in PPAR-α knockout (PPAR-α(-/-)) animals, mice were treated in different regimes: mice received chow enriched with or without WY for 14 days prior AEC isolation (in-vivo treatment). Furthermore, isolated AEC from both groups were subsequently cultured with or without WY (in-vitro treatment). AEC were stimulated with lipopolysaccharide (LPS). Cell culture supernatant and cell lysate were used for analysis of pro-inflammatory mediators. AEC challenged with LPS showed a significantly increased generation of pro-inflammatory mediators. After in-vivo WY-exposure, AEC displayed significantly reduced concentration of TNF-α, MIP-2, and TxB2 after LPS stimulation. This beneficial effect was abrogated in PPAR-α(-/-) animals. Interestingly, sole in-vitro application of WY-14643 failed to reduce levels of pro-inflammatory mediators whereas we found an additive effect of a combined in-vivo and in-vitro PPAR-α activation. PGE2 concentration remained high after LPS challenge and was unaffected by WY treatment. PPAR-α activation by in-vivo exposure to fibrates reduced the inflammatory response in isolated AEC. These findings may facilitate further studies investigating the translation of pharmacological PPAR-α activation into clinical therapy of ARDS.
    Experimental Lung Research 07/2015; DOI:10.3109/01902148.2015.1046200 · 1.75 Impact Factor
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    ABSTRACT: Influenza A viruses (IAV) pose a constant threat to the human population and therefore a better understanding of their fundamental biology and identification of novel therapeutics is of upmost importance. Various reporter-encoding IAV were generated to achieve these goals, however, one recurring difficulty was the genetic instability especially of larger reporter genes. We employed the viral NS segment coding for the non-structural protein 1 (NS1) and nuclear export protein (NEP) for stable expression of diverse reporter proteins. This was achieved by converting the NS segment into a single open reading frame (ORF) coding for NS1, the respective reporter and NEP. To allow expression of individual proteins, the reporter genes were flanked by two porcine Teschovirus-1 2A peptide (PTV-1 2A)-coding sequences. The resulting viruses encoding luciferases, fluorescent proteins or a Cre recombinase are characterized by a high genetic stability in vitro and in mice and can be readily employed for antiviral compound screenings, visualization of infected cells or cells that survived acute infection.
    Scientific Reports 06/2015; 5:11346. DOI:10.1038/srep11346 · 5.58 Impact Factor
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    ABSTRACT: Impaired immune function contributes to the development of chronic obstructive pulmonary disease (COPD). Disease progression is further exacerbated by pathogen infections due to impaired immune responses. Elimination of infected cells is achieved by cytotoxic CD8(+) T cells that are activated by MHC I-mediated presentation of pathogen-derived antigenic peptides. The immunoproteasome, a specialized form of the proteasome, improves generation of antigenic peptides for MHC I presentation thereby facilitating anti-viral immune responses. However, immunoproteasome function in the lung has not been investigated in detail yet. In this study, we comprehensively characterized the function of immunoproteasomes in the human and murine lung. Parenchymal cells of the lung express low constitutive levels of immunoproteasomes, while they are highly and specifically expressed in alveolar macrophages. Immunoproteasome expression is not altered in whole lung tissue of COPD patients. Novel activity-based probes and native gel analysis revealed that immunoproteasome activities are specifically and rapidly induced by IFNγ treatment in respiratory cells in vitro and by virus infection of the lung in mice. Our results suggest that the lung is potentially capable of mounting an immunoproteasome-mediated efficient adaptive immune response to intracellular infections.
    Scientific Reports 05/2015; 5:10230. DOI:10.1038/srep10230 · 5.58 Impact Factor
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    ABSTRACT: Acute respiratory distress syndrome (ARDS) is a major cause of mortality in intensive care units. As there is raising evidence about immuno-modulatory effects of lipid emulsions required for parenteral nutrition of ARDS patients, we sought to investigate whether infusion of conventional soybean oil (SO)-based or fish oil (FO)-based lipid emulsions rich in either n-6 or n-3 fatty acids, respectively, may influence subsequent pulmonary inflammation. In a randomized controlled, single-blinded pilot study, forty-two volunteers received SO, FO, or normal saline for two days. Thereafter, volunteers inhaled pre-defined doses of lipopolysaccharide (LPS) followed by bronchoalveolar lavage (BAL) 8 or 24 h later. In the murine model of LPS-induced lung injury a possible involvement of resolvin E1 (RvE1) receptor ChemR23 was investigated. Wild-type and ChemR23 knockout mice were infused with both lipid emulsions and challenged with LPS intratracheally. In volunteers receiving lipid emulsions, the fatty acid profile in the plasma and in isolated neutrophils and monocytes was significantly changed. Adhesion of isolated monocytes to endothelial cells was enhanced after infusion of SO and reduced by FO, however, no difference of infusion on an array of surface adhesion molecules was detected. In neutrophils and monocytes, LPS-elicited generation of pro-inflammatory cytokines increased in the SO and decreased in the FO group. LPS inhalation in volunteers evoked an increase in neutrophils in BAL fluids, which decreased faster in the FO group. While TNF-α in the BAL was increased in the SO group, IL-8 decreased faster in the FO group. In the murine model of lung injury, effects of FO similar to the volunteer group observed in wild-type mice were abrogated in ChemR23 knockout mice. After infusion of conventional lipid emulsions, leukocytes exhibited increased adhesive and pro-inflammatory features. In contrast, FO-based lipid emulsions reduced monocyte adhesion, decreased pro-inflammatory cytokines, and neutrophil recruitment into the alveolar space possibly mediated by ChemR23-signaling. Lipid emulsions thus exert differential effects in human volunteers and mice in vivo. DRKS00006131 at the German Clinical Trial Registry, 2014/05/14.
    Critical care (London, England) 05/2015; 19(1):226. DOI:10.1186/s13054-015-0933-6
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    ABSTRACT: Maturation of the lung extracellular matrix (ECM) plays an important role in the formation of alveolar gas exchange units. A key step in ECM maturation is cross-linking of collagen and elastin, which imparts stability and functionality to the ECM. During aberrant late lung development in bronchopulmonary dysplasia (BPD) patients and animal models of BPD, alveolarization is blocked, and the function of ECM cross-linking enzymes is deregulated, suggesting that perturbed ECM cross-linking may impact alveolarization. In a hyperoxia (85% O2)-based mouse model of BPD, blunted alveolarization was accompanied by alterations to lung collagen and elastin levels and cross-linking. Total collagen levels were increased (by 63%). The abundance of dihydroxylysinonorleucine collagen cross-links and the dihydroxylysinonorleucine/hydroxylysinonorleucine ratio were increased by 11% and 18%, respectively; suggestive of a pro fibrotic state. In contrast, insoluble elastin levels and the abundance of the elastin cross-links desmosine and isodesmosine in insoluble elastin were decreased by 35%, 30%, and 21%, respectively. The lung collagen/elastin ratio was three fold increased. Treatment of hyperoxia-exposed newborn mice with the lysyl oxidase inhibitor β-aminopropionitrile (BAPN) partially restored normal collagen levels, normalized the dihydroxylysinonorleucine/hydroxylysinonorleucine ratio, partially normalized desmosine and isodesmosine cross-links in insoluble elastin, and partially restored elastin foci structure in the developing septa. However, BAPN administration concomitant with hyperoxia exposure did not improve alveolarization, evident from unchanged alveolar surface area and alveoli number, and worsened septal thickening (increased by 12%). These data demonstrate that collagen and elastin cross-linking are perturbed during the arrested alveolarization of developing mouse lungs exposed to hyperoxia. Copyright © 2015, American Journal of Physiology - Lung Cellular and Molecular Physiology.
    AJP Lung Cellular and Molecular Physiology 04/2015; 308(11):ajplung.00039.2015. DOI:10.1152/ajplung.00039.2015 · 4.04 Impact Factor
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    ABSTRACT: Fibroblast growth factors (Fgfs) mediate organ repair. Lung epithelial cell overexpression of Fgf10 post-bleomycin injury is both protective and therapeutic, characterized by increased survival and attenuated fibrosis. Exogenous administration of FGF7 (Palifermin) also showed prophylactic survival benefits in mice. The role of endogenous Fgfr2b ligands upon bleomycin-induced lung fibrosis is still elusive. This study reports the expression of endogenous Fgfr2b ligands, receptors and signaling targets in wild type mice following bleomycin lung injury. In addition, the impact of attenuating endogenous Fgfr2b-ligands following bleomycin-induced fibrosis was tested using a doxycycline (dox)-based inducible, soluble, dominant-negative form of the Fgfr2b receptor. Double transgenic (DTG) Rosa26(rtTA/+);tet(O)solFgfr2b mice were validated for the expression and activity of soluble Fgfr2b (failure to regenerate maxillary incisors, attenuated recombinant FGF7 signal in the lung). As previously reported, no defects in lung morphometry were detected in DTG (+dox) mice exposed from post-natal (PN) 1 through PN105. Female single transgenic (STG) and DTG mice were subjected to various levels of bleomycin injury (1.0, 2.0, and 3.0U/kg). Fgfr2b ligands were attenuated either throughout injury (d0-d11; d0-28) or during later stages (d6-d28 and d14-d28). No significant changes in survival, weight, lung function, confluent areas of fibrosis, or hydroxyproline deposition were detected in DTG mice. These results indicate that endogenous Fgfr2b ligands do not significantly protect against bleomycin injury, nor do they expedite the resolution of bleomycin lung induced injury in mice. Copyright © 2014, American Journal of Physiology - Lung Cellular and Molecular Physiology.
    AJP Lung Cellular and Molecular Physiology 03/2015; 308(10):ajplung.00291.2014. DOI:10.1152/ajplung.00291.2014 · 4.04 Impact Factor
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    ABSTRACT: Influenza A virus (IAV) replicates its segmented RNA genome in the nucleus of infected cells and utilizes caspase-dependent nucleocytoplasmic export mechanisms to transport newly formed ribonucleoprotein complexes (RNPs) to the site of infectious virion release at the plasma membrane. In this study, we obtained evidence that apoptotic caspase activation in IAV-infected cells is associated with the degradation of the nucleoporin Nup153, an integral subunit of the nuclear pore complex. Transmission electron microscopy studies revealed a distinct enlargement of nuclear pores in IVA-infected cells. Transient expression and subcellular accumulation studies of multimeric marker proteins in virus-infected cells provided additional evidence for increased nuclear pore diameters facilitating the translocation of large protein complexes across the nuclear membrane. Furthermore, caspase 3/7 inhibition data obtained in this study suggest that active, Crm1-dependent IAV RNP export mechanisms are increasingly complemented by passive, caspase-induced export mechanisms at later stages of infection. In contrast to most other RNA viruses, influenza virus genome replication occurs in the nucleus (rather than cytoplasm) of infected cells. Therefore, completion of the viral replication cycle critically depends on intracellular transport mechanisms that ensure the translocation of viral ribonucleoprotein (RNP) complexes across the nuclear membrane. Here, we demonstrate that virus-induced cellular caspase activities cause a widening of nuclear pores, thereby facilitating nucleocytoplasmic translocation processes and, possibly, promoting nuclear export of newly synthesized RNPs. These passive transport mechanisms are suggested to complement Crm1-dependent RNP export mechanisms known to occur at early stages of the replication cycle and may contribute to highly efficient production of infectious virus progeny at late stages of the viral replication cycle. The study provides an intriguing example of how influenza virus exploits cellular structures and regulatory pathways, including intracellular transport mechanisms, to complete its replication cycle and maximize the production of infectious virus progeny. Copyright © 2015, American Society for Microbiology. All Rights Reserved.
    Journal of Virology 03/2015; 89(11). DOI:10.1128/JVI.03531-14 · 4.65 Impact Factor
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    ABSTRACT: The influenza viruses are some of the most important human pathogens, causing substantial seasonal and pandemic morbidity and mortality. In humans, infection of the lower respiratory tract of can result in flooding of the alveolar compartment, development of acute respiratory distress syndrome and death from respiratory failure. Influenza-mediated damage of the airway, alveolar epithelium and alveolar endothelium results from a combination of: 1) intrinsic viral pathogenicity, attributable to its tropism for host airway and alveolar epithelial cells; and 2) a robust host innate immune response, which, while contributing to viral clearance, can worsen the severity of lung injury. In this review, we summarise the molecular events at the virus-host interface during influenza virus infection, highlighting some of the important cellular responses. We discuss immune-mediated viral clearance, the mechanisms promoting or perpetuating lung injury, lung regeneration after influenza-induced injury, and recent advances in influenza prevention and therapy. Copyright ©ERS 2015.
    European Respiratory Journal 03/2015; 45(5). DOI:10.1183/09031936.00186214 · 7.13 Impact Factor
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    ABSTRACT: Rationale: Recent studies indicate that tumor associated macrophages with an M2 phenotype can influence cancer progression and metastasis, but the regulatory pathways remain poorly characterized. Objectives: This study investigated the role of tumor-associated macrophages (MΦ) in lung cancer. Methods and results: Co-culturing of MΦ with mouse Lewis Lung Carcinoma (LLC1) and 10 different human lung cancer cell lines (adenocarcinoma, squamous and large cell carcinoma) caused upregulation of CCR2/CCL2 and CX3CR1/CX3CL1 in both the cancer cells and the MΦ. In the MΦ-tumor cell system, IL-10 drove CCR2 and CX3CR1 upregulation, while CCL1, G-CSF and MIP1α were required for the upregulation of CCL2 and CX3CL1. Downstream phenotypic effects included enhanced LLC1 proliferation and migration and MΦ M2 polarization. In vivo, MΦ depletion (clodronate, MaFIA mice) and genetic ablation of CCR2 and CX3CR1 all inhibited LLC1 tumor growth and metastasis, shifted tumor-associated MΦ towards M1 polarization, suppressed tumor vessel growth and enhanced survival (metastasis model). Furthermore, mice treated with CCR2 antagonist mimicked genetic ablation of CCR2 by reducing tumor growth and metastasis. In human lung cancer samples, tumor MΦ infiltration and CCR2 expression correlated with tumor stage and metastasis. Conclusions: Tumor-associated MΦ play a central role in lung cancer growth and metastasis, with bidirectional crosstalk between MΦ and cancer cells via CCR2- and CX3CR1-signaling as an central underlying mechanism. These findings suggest that the therapeutic strategy of blocking CCR2 and CX3CR1 may prove beneficial for halting lung cancer progression.
    American Journal of Respiratory and Critical Care Medicine 12/2014; 191(4). DOI:10.1164/rccm.201406-1137OC · 11.99 Impact Factor
  • Stephan Ludwig · Roland Zell · Martin Schwemmle · Susanne Herold
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    ABSTRACT: Influenza virus is a paradigm for a pathogen that frequently crosses the species barrier from animals to humans, causing severe disease in the human population. This ranges from frequent epidemics to occasional pandemic outbreaks with millions of death. All previous pandemics in humans were caused by animal viruses or virus reassortants carrying animal virus genes, underlining that the fight against influenza requires a One Health approach integrating human and veterinary medicine. Furthermore, the fundamental question of what enables a flu pathogen to jump from animals to humans can only be tackled in a transdisciplinary approach between virologists, immunologists and cell biologists. To address this need the German FluResearchNet was established as a first nationwide influenza research network that virtually integrates all national expertise in the field of influenza to unravel viral and host determinants of pathogenicity and species transmission and to explore novel avenues of antiviral intervention. Here we focus on the various novel anti-flu approaches that were developed as part of the FluResearchNet activities.
    International Journal of Medical Microbiology 08/2014; 304(7). DOI:10.1016/j.ijmm.2014.08.016 · 3.42 Impact Factor
  • Pneumologie; 06/2014
  • Pneumologie 06/2014; 68(06). DOI:10.1055/s-0034-1376793
  • Pneumologie 06/2014; 68(06). DOI:10.1055/s-0034-1376802
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    ABSTRACT: Pulmonary vascular remodeling, the pathological hallmark of pulmonary arterial hypertension, is attributed to proliferation, apoptosis resistance, and migration of vascular cells. A role of dysregulated matrix cross-linking and stability as a pathogenic mechanism has received little attention. We aimed to assess whether matrix cross-linking enzymes played a causal role in experimental pulmonary hypertension (PH). All 5 lysyl oxidases were detected in concentric and plexiform vascular lesions of patients with idiopathic pulmonary arterial hypertension. Lox, LoxL1, LoxL2, and LoxL4 expression was elevated in lungs of patients with idiopathic pulmonary arterial hypertension, whereas LoxL2 and LoxL3 expression was elevated in laser-capture microdissected vascular lesions. Lox expression was hypoxia-responsive in pulmonary artery smooth muscle cells and adventitial fibroblasts, whereas LoxL1 and LoxL2 expression was hypoxia-responsive in adventitial fibroblasts. Lox expression was increased in lungs from hypoxia-exposed mice and in lungs and pulmonary artery smooth muscle cells of monocrotaline-treated rats, which developed PH. Pulmonary hypertensive mice exhibited increased muscularization and perturbed matrix structures in vessel walls of small pulmonary arteries. Hypoxia exposure led to increased collagen cross-linking, by dihydroxylysinonorleucine and hydroxylysinonorleucine cross-links. Administration of the lysyl oxidase inhibitor β-aminopropionitrile attenuated the effect of hypoxia, limiting perturbations to right ventricular systolic pressure, right ventricular hypertrophy, and vessel muscularization and normalizing collagen cross-linking and vessel matrix architecture. Lysyl oxidases are dysregulated in clinical and experimental PH. Lysyl oxidases play a causal role in experimental PH and represent a candidate therapeutic target. Our proof-of-principle study demonstrated that modulation of lung matrix cross-linking can affect pulmonary vascular remodeling associated with PH.
    Arteriosclerosis Thrombosis and Vascular Biology 05/2014; 34(7). DOI:10.1161/ATVBAHA.114.303534 · 5.53 Impact Factor
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    ABSTRACT: Acute respiratory distress syndrome (ARDS) is a major cause of mortality in intensive care units. Patients with ARDS often require parenteral nutrition with lipid emulsions as essential components. Besides energy supply these lipid emulsions might display differential modulatory effects on lung integrity and inflammation. In a pre-emptive strategy, we investigated the impact of three different intravenously infused lipid emulsions on lung morphology, leukocyte invasion, protein leakage and cytokines in a murine model of ARDS. Mice received an infusion of normal saline solution, pure long-chain triglycerides (LCT) emulsion, a medium-chain triglycerides (MCT) containing mixed emulsion (LCT/MCT), or a fish-oil (FO) containing mixed emulsion (LCT/MCT/FO) before lipopolysaccharide (LPS) challenge. Mice pre-infused with fish-oil containing lipid emulsion showed decreased leukocyte invasion, protein leakage, myeloperoxidase activity, and cytokine production in their alveolar space after LPS challenge compared to mice receiving LCT or LCT/MCT. In line with these findings lung morphology assessed by histological staining after LPS-induced lung injury improved faster in the LCT/MCT/FO group. Concerning above mentioned parameters no significant difference was observed between mice infused with LCT or the combination of LCT and MCT. Fish oil-containing lipid emulsions might exert anti-inflammatory and pro-resolving effects in the murine model of acute lung injury. Partial replacement of n-6 fatty acids with n-3 fatty acids may thus be of benefit for critically ill patients at risk for ARDS which require parenteral nutrition.
    Critical care (London, England) 04/2014; 18(2):R85. DOI:10.1186/cc13850
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    ABSTRACT: Castleman's disease, also known as angiofollicular lymph node hyperplasia, is a rare disease with two known expansion types, unicentric and multicentric, which play a major role in determining therapy. We focus here on the unicentric type, which can be treated and cured by surgery. To date, approximately 1000 cases of Castleman's disease have been reported in the literature. A 50-year-old Caucasian woman presented to our Department of Hematology and Internal Oncology with increasing fatigue as her sole symptom. Diagnostic investigations including laboratory studies, ultrasound, computed tomography and magnetic resonance imaging were performed. These revealed an interaortocaval, retroperitoneal tumor mass in her upper abdomen as the only manifestation of the disease. No enlarged lymph nodes were detected. We conducted a laparotomy with radical extirpation of the tumor mass (10x9x5.7cm). Complete tumor resection with clear margins was achieved. A pathological analysis of the resected sample showed atypical lymphoid tissue of small to medium cells with some clearly visible nucleoli, enlarged sinusoidal vessels, pleomorphic calcifications and focally preserved germinal-center-like structures. Histological and immunohistochemical analysis confirmed the diagnosis of Castleman's disease: staining for CD3, CD5, CD10, CD20, CD23, CD79 and Ki-67 was strongly positive in the germinal-center-like structures. Histological findings clearly showed the disease to be the hyaline vascular subtype. Staining for cyclin D1 and CD30 was negative. Expression of CD15 was positive in the enlarged sinusoidal vessels. A supplementary clonality analysis was without pathological findings. Tests for human immunodeficiency virus and human herpes virus 8 were negative and results from a bone marrow biopsy were normal. Our patient recovered well from surgery and was discharged from our hospital. To date, no recurrence of the disease has been detected. Castleman's disease is a rare disorder that remains a diagnostic challenge. Radical surgical resection is considered to be the gold standard for treating the unicentric variant of this disease.
    Journal of Medical Case Reports 03/2014; 8(1):93. DOI:10.1186/1752-1947-8-93
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    ABSTRACT: Aberrant remodelling of the extracellular matrix in the developing lung may underlie arrested alveolarisation associated with bronchopulmonary dysplasia (BPD). Transglutaminases are regulators of extracellular matrix remodelling. Therefore, the expression and activity of transglutaminases were assessed in lungs from human neonates with BPD and in a rodent model of BPD.Transglutaminase expression and localisation were assessed by RT-PCR, immunoblotting, activity assay and immunohistochemical analyses of human and mouse lung tissues. Transglutaminase regulation by transforming growth factor (TGF)-β was investigated in lung cells by luciferase-based reporter assay and RT-PCR. TGF-β signalling was neutralised in vivo in an animal model of BPD, to determine whether TGF-β mediated the hyperoxia-induced changes in transglutaminase expression.Transglutaminase 2 expression was upregulated in the lungs of preterm infants with BPD and in the lungs of hyperoxia-exposed mouse pups, where lung development was arrested. Transglutaminase 2 localised to the developing alveolar septa. TGF-β was identified as a regulator of transglutaminase 2 expression in human and mouse lung epithelial cells. In vivo neutralisation of TGF-β signalling partially restored normal lung structure and normalised lung transglutaminase 2 mRNA expression.Our data point to a role for perturbed transglutaminase 2 activity in the arrested alveolarisation associated with BPD.
    European Respiratory Journal 03/2014; 44(1). DOI:10.1183/09031936.00075713 · 7.13 Impact Factor
  • American Journal of Respiratory and Critical Care Medicine 03/2014; 189(5):609-11. DOI:10.1164/rccm.201311-2041LE · 11.99 Impact Factor
  • Susanne Herold · Claudia A Staab-Weijnitz
    American Journal of Respiratory and Critical Care Medicine 02/2014; 189(4):386-9. DOI:10.1164/rccm.201401-0063ED · 11.99 Impact Factor