scholarly journals Tenascin-C: Friend or Foe in Lung Aging?

2021 ◽  
Vol 12 ◽  
Author(s):  
Sandrine Gremlich ◽  
Tiziana P. Cremona ◽  
Eveline Yao ◽  
Farah Chabenet ◽  
Kleanthis Fytianos ◽  
...  
Keyword(s):  
Pulmonary Function ◽  
Smooth Muscle Actin ◽  
Lung Parenchyma ◽  
Normal Lung ◽  
Matricellular Protein ◽  
Ecm Remodeling ◽  
Tenascin C ◽  
Lung Structure ◽  
Regulatory Functions ◽  
Lung Aging

Lung aging is characterized by lung function impairment, ECM remodeling and airspace enlargement. Tenascin-C (TNC) is a large extracellular matrix (ECM) protein with paracrine and autocrine regulatory functions on cell migration, proliferation and differentiation. This matricellular protein is highly expressed during organogenesis and morphogenetic events like injury repair, inflammation or cancer. We previously showed that TNC deficiency affected lung development and pulmonary function, but little is known about its role during pulmonary aging. In order to answer this question, we characterized lung structure and physiology in 18 months old TNC-deficient and wild-type (WT) mice. Mice were mechanically ventilated with a basal and high tidal volume (HTV) ventilation protocol for functional analyses. Additional animals were used for histological, stereological and molecular biological analyses. We observed that old TNC-deficient mice exhibited larger lung volume, parenchymal volume, total airspace volume and septal surface area than WT, but similar mean linear intercept. This was accompanied by an increase in proliferation, but not apoptosis or autophagy markers expression throughout the lung parenchyma. Senescent cells were observed in epithelial cells of the conducting airways and in alveolar macrophages, but equally in both genotypes. Total collagen content was doubled in TNC KO lungs. However, basal and HTV ventilation revealed similar respiratory physiological parameters in both genotypes. Smooth muscle actin (α-SMA) analysis showed a faint increase in α-SMA positive cells in TNC-deficient lungs, but a marked increase in non-proliferative α-SMA + desmin + cells. Major TNC-related molecular pathways were not up- or down-regulated in TNC-deficient lungs as compared to WT; only minor changes in TLR4 and TGFβR3 mRNA expression were observed. In conclusion, TNC-deficient lungs at 18 months of age showed exaggerated features of the normal structural lung aging described to occur in mice between 12 and 18 months of age. Correlated to the increased pulmonary function parameters previously observed in young adult TNC-deficient lungs and described to occur in normal lung aging between 3 and 6 months of age, TNC might be an advantage in lung aging.

Antifibrotic properties of caveolin-1 scaffolding domain in vitro and in vivo

2008 ◽  
Vol 294 (5) ◽  
pp. L843-L861 ◽  
Author(s):  
Elena Tourkina ◽  
Mathieu Richard ◽  
Pal Gööz ◽  
Michael Bonner ◽  
Jaspreet Pannu ◽  
...  
Keyword(s):  
Lung Fibrosis ◽  
Smooth Muscle Actin ◽  
Lung Fibroblasts ◽  
Normal Lung ◽  
Signaling Molecule ◽  
Caveolin 1 ◽  
Tenascin C ◽  
Ecm Proteins

Lung fibrosis involves the overexpression of ECM proteins, primarily collagen, by α-smooth muscle actin (ASMA)-positive cells. Caveolin-1 is a master regulator of collagen expression by cultured lung fibroblasts and of lung fibrosis in vivo. A peptide equivalent to the caveolin-1 scaffolding domain (CSD peptide) inhibits collagen and tenascin-C expression by normal lung fibroblasts (NLF) and fibroblasts from the fibrotic lungs of scleroderma patients (SLF). CSD peptide inhibits ASMA expression in SLF but not NLF. Similar inhibition of collagen, tenascin-C, and ASMA expression was also observed when caveolin-1 expression was upregulated using adenovirus. These observations suggest that the low caveolin-1 levels in SLF cause their overexpression of collagen, tenascin-C, and ASMA. In mechanistic studies, MEK, ERK, JNK, and Akt were hyperactivated in SLF, and CSD peptide inhibited their activation and altered their subcellular localization. These studies and experiments using kinase inhibitors suggest many differences between NLF and SLF in signaling cascades. To validate these data, we determined that the alterations in signaling molecule activation observed in SLF also occur in fibrotic lung tissue from scleroderma patients and in mice with bleomycin-induced lung fibrosis. Finally, we demonstrated that systemic administration of CSD peptide to bleomycin-treated mice blocks epithelial cell apoptosis, inflammatory cell infiltration, and changes in tissue morphology as well as signaling molecule activation and collagen, tenascin-C, and ASMA expression associated with lung fibrosis. CSD peptide may be a prototype for novel treatments for human lung fibrosis that act, in part, by inhibiting the expression of ASMA and ECM proteins.

scholarly journals Beyond Bronchiolitis Obliterans: In-Depth Histopathologic Characterization of Bronchiolitis Obliterans Syndrome after Lung Transplantation

2021 ◽  
Vol 11 (1) ◽  
pp. 111
Author(s):  
Arno Vanstapel ◽  
Stijn E. Verleden ◽  
Eric K. Verbeken ◽  
Peter Braubach ◽  
Tinne Goos ◽  
...  
Keyword(s):  
Lung Transplantation ◽  
Bronchiolitis Obliterans ◽  
Lung Parenchyma ◽  
Bronchiolitis Obliterans Syndrome ◽  
Normal Lung ◽  
Consensus Guidelines ◽  
Vascular Abnormalities ◽  
Lung Structure ◽  
Histopathologic Findings

Bronchiolitis obliterans syndrome (BOS) is considered an airway-centered disease, with bronchiolitis obliterans (BO) as pathologic hallmark. However, the histologic spectrum of pure clinical BOS remains poorly characterized. We provide the first in-depth histopathologic description of well-characterized BOS patients and patients without chronic lung allograft dysfunction (CLAD), defined according to the recent consensus guidelines. Explant lung tissue from 52 clinically-defined BOS and 26 non-CLAD patients (collected 1993–2018) was analyzed for histologic parameters, including but not limited to airway lesions, vasculopathy and fibrosis. In BOS, BO lesions were evident in 38 (73%) patients and varied from concentric sub-epithelial fibrotic BO to inflammatory BO, while 10/14 patients without BO displayed ‘vanishing airways’, defined by a discordance between arteries and airways. Chronic vascular abnormalities were detected in 22 (42%) patients. Ashcroft fibrosis scores revealed a median of 43% (IQR: 23–69) of normal lung parenchyma per patient; 26% (IQR: 18–37) of minimal alveolar fibrous thickening; and 11% (IQR: 4–18) of moderate alveolar thickening without architectural damage. Patchy areas of definite fibrotic damage to the lung structure (i.e., Ashcroft score ≥ 5) were present in 28 (54%) patients. Fibrosis was classified as bronchocentric (n = 21/28, 75%), paraseptal (n = 17/28, 61%) and subpleural (n = 15/28, 54%). In non-CLAD patients, BO lesions were absent, chronic vascular abnormalities present in 1 (4%) patient and mean Ashcroft scores were significantly lower compared to BOS (p = 0.0038) with 78% (IQR:64–88) normally preserved lung parenchyma. BOS explant lungs revealed evidence of various histopathologic findings, including vasculopathy and fibrotic changes, which may contribute to the pathophysiology of BOS.

Il-17A contributes to maintenance of pulmonary homeostasis in a murine model of cigarette smoke-induced emphysema

2015 ◽  
Vol 309 (2) ◽  
pp. L188-L195 ◽  
Author(s):  
Meike Voss ◽  
Lisa Wolf ◽  
Andreas Kamyschnikow ◽  
Bodo Wonnenberg ◽  
Anja Honecker ◽  
...  
Keyword(s):  
Pulmonary Function ◽  
Cigarette Smoke ◽  
Murine Model ◽  
Lung Damage ◽  
Disease Assessment ◽  
Normal Lung ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Lung Structure ◽  
Induced Changes

Smoking is the main risk factor for the development of the chronic obstructive pulmonary disease (COPD) in Western countries. Recent studies suggest that IL-17A and Th17 cells play a role in the pathogenesis of COPD. We used a murine model of chronic cigarette smoke (CS) exposure to explore the contribution of IL-17A to CS-induced lung damage and loss of pulmonary function. Histology and morphometry showed that IL-17A deficiency spontaneously resulted in a loss of lung structure under basal conditions. Even though inflammatory markers [IL-1β and granulocyte colony-stimulating factor (G-CSF)] were decreased in IL-17A-deficient mice (IL-17A−/−) exposed to CS compared with wild-type (WT) mice, IL-17A−/− mice were per se not protected from CS-induced emphysematous disease. Assessment of pulmonary function showed that IL-17A−/− mice were partially protected from CS-induced changes in total lung capacity. However, the respiratory elastance decreased and respiratory compliance increased in IL-17A−/− mice after exposure to CS. Morphometry revealed destruction of lung tissue in CS-exposed IL-17A−/− mice similar to WT mice. The expression of elastin was decreased in air-exposed IL-17A−/− mice and in CS-exposed WT and IL-17A−/− mice. Thus, in the present model of sterile CS-exposure, IL-17A contributes to normal lung homeostasis and does not mediate CS-induced loss of lung structure and pulmonary function.

Normal Lung Structure and Pulmonary Function in a Twin with Agenesis of the Cloacal Membrane and Persistent Severe Oligohydramnios

1992 ◽  
Vol 1 (1) ◽  
pp. 24-28 ◽  
Author(s):  
David M. Sherer ◽  
David M. Sherer ◽  
Susan A. Smith ◽  
Carol L. Cusson ◽  
Leon A. Metlay ◽  
...  
Keyword(s):  
Pulmonary Function ◽  
Normal Lung ◽  
Cloacal Membrane ◽  
Lung Structure

scholarly journals Tenascin-C in Heart Diseases—The Role of Inflammation

2021 ◽  
Vol 22 (11) ◽  
pp. 5828
Author(s):  
Kyoko Imanaka-Yoshida
Keyword(s):  
Ventricular Remodeling ◽  
Heart Diseases ◽  
Genetically Engineered ◽  
Matricellular Protein ◽  
Myocardial Repair ◽  
Inflammatory Reactions ◽  
Tenascin C ◽  
Genetically Engineered Mice

Tenascin-C (TNC) is a large extracellular matrix (ECM) glycoprotein and an original member of the matricellular protein family. TNC is transiently expressed in the heart during embryonic development, but is rarely detected in normal adults; however, its expression is strongly up-regulated with inflammation. Although neither TNC-knockout nor -overexpressing mice show a distinct phenotype, disease models using genetically engineered mice combined with in vitro experiments have revealed multiple significant roles for TNC in responses to injury and myocardial repair, particularly in the regulation of inflammation. In most cases, TNC appears to deteriorate adverse ventricular remodeling by aggravating inflammation/fibrosis. Furthermore, accumulating clinical evidence has shown that high TNC levels predict adverse ventricular remodeling and a poor prognosis in patients with various heart diseases. Since the importance of inflammation has attracted attention in the pathophysiology of heart diseases, this review will focus on the roles of TNC in various types of inflammatory reactions, such as myocardial infarction, hypertensive fibrosis, myocarditis caused by viral infection or autoimmunity, and dilated cardiomyopathy. The utility of TNC as a biomarker for the stratification of myocardial disease conditions and the selection of appropriate therapies will also be discussed from a clinical viewpoint.

scholarly journals Lamin A/C Mechanosensor Drives Tumor Cell Aggressiveness and Adhesion on Substrates With Tissue-Specific Elasticity

2021 ◽  
Vol 9 ◽  
Author(s):  
Enrica Urciuoli ◽  
Valentina D’Oria ◽  
Stefania Petrini ◽  
Barbara Peruzzi
Keyword(s):  
Tumor Cell ◽  
Tumor Cells ◽  
Lung Parenchyma ◽  
Normal Lung ◽  
Lamin A ◽  
Osteosarcoma Cell ◽  
Adhesion Properties ◽  
Tissue Specific ◽  
Definition Of ◽  
High Level

Besides its structural properties in the nucleoskeleton, Lamin A/C is a mechanosensor protein involved in perceiving the elasticity of the extracellular matrix. In this study we provide evidence about Lamin A/C-mediated regulation of osteosarcoma cell adhesion and spreading on substrates with tissue-specific elasticities. Our working hypothesis is based on the observation that low-aggressive and bone-resident SaOS-2 osteosarcoma cells express high level of Lamin A/C in comparison to highly metastatic, preferentially to the lung, osteosarcoma 143B cells, thereby suggesting a role for Lamin A/C in tumor cell tropism. Specifically, LMNA gene over-expression in 143B cells induced a reduction in tumor cell aggressiveness in comparison to parental cells, with decreased proliferation rate and reduced migration capability. Furthermore, LMNA reintegration into 143B cells changed the adhesion properties of tumor cells, from a preferential tropism toward the 1.5 kPa PDMS substrate (resembling normal lung parenchyma) to the 28 kPa (resembling pre-mineralized bone osteoid matrix). Our study suggests that Lamin A/C expression could be involved in the organ tropism of tumor cells, thereby providing a rationale for further studies focused on the definition of cancer mechanism of metastatization.

scholarly journals Longitudinal Assessment of Pulmonary Function and Bronchodilator Response in Pediatric Patients With Post-infectious Bronchiolitis Obliterans

2021 ◽  
Vol 9 ◽  
Author(s):  
Xiuhua Yu ◽  
Jiaoyang Wei ◽  
Yanchun Li ◽  
Lu Zhang ◽  
Hongming Che ◽  
...  
Keyword(s):  
Pulmonary Function ◽  
Bronchiolitis Obliterans ◽  
Pediatric Patients ◽  
Average Rate ◽  
Pulmonary Function Tests ◽  
Case Series ◽  
Lung Parenchyma ◽  
Forced Expiratory Volume ◽  
Longitudinal Assessment ◽  
Bronchodilator Response

Backgroud: Postinfectious bronchiolitis obliterans (PIBO) is a rare respiratory disease. In recent years, the disease has been recognized and diagnosed increasingly in children. Pulmonary function is important for diagnosis, identifying the severity of the PIBO and monitoring progression. But there have been only a few studies that followed the evolution of PIBO on the basis of pulmonary function tests (PFTs).Objective: The study targeted the evolution of pulmonary function and bronchodilator response in a case series of Chinese children with PIBO.Methods: Twelve children between the ages of 6–99 months with PIBO were studied retrospectively from 2009 to 2019. Forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1), the FEV1/FVC ratio, and maximal midexpiratory flow velocity 25–75% (MMEF25−75%) were collected at each PFT, and bronchodilator responses were evaluated. Spirometric parameters were monitored over time, and generalized linear mixed models were used to analyze longitudinal panel data.Results: The median baseline PFT values for FVC, FEV1, the FEV1/FVC ratio, and MMEF25−75% were 41.6, 39.75, 90.7, and 22.2%, respectively. At the initial PFTs, 10 (83.3%) patients demonstrated a significant bronchodilator response. FVC and FEV1 increased by 8.212%/year and 5.007%/year, respectively, and the FEV1/FVC ratio decreased by an average of 3.537%/year. MMEF25−75% showed improvement at an average rate of 1.583% every year. Overall, FEV1 and MMEF25−75% showed different degrees of improvement after the use of inhaled bronchodilators at each PFT session for 10 patients, and FEV1 measures demonstrated significant (>12%) β2-bronchodilation in 56% of PFT sessions.Conclusions: Pediatric patients with PIBO showed an obstructive defect in pulmonary function. The FVC, FEV1, and MMEF25−75% improved as they grew older, while the FEV1/FVC ratio decreased. This may be due to the development of lung parenchyma more than airway growth. Airway obstruction in some patients improved with the use of β2 agonists.

A vision transformer for emphysema classification using CT images

2021 ◽  
Author(s):  
Yanan Wu ◽  
Shouliang Qi ◽  
Yu Sun ◽  
Shuyue Xia ◽  
Yudong Yao ◽  
...  
Keyword(s):  
Lung Parenchyma ◽  
Ct Images ◽  
Normal Lung ◽  
Massive Data ◽  
Large Patch ◽  
The Public ◽  
Evaluation Approach ◽  
Average Accuracy ◽  
Public Dataset ◽  
Aided Diagnosis

Abstract Objective: Emphysema is characterized by the destruction and permanent enlargement of the alveoli in the lung. According to visual CT appearance, emphysema can be divided into three subtypes: centrilobular emphysema (CLE), panlobular emphysema (PLE), and paraseptal emphysema (PSE). Automating emphysema classification can help precisely determine the patterns of lung destruction and provide a quantitative evaluation. Approach: We propose a vision transformer (ViT) model to classify the emphysema subtypes via CT images. First, large patches (61×61) are cropped from CT images which contain the area of normal lung parenchyma (NLP), CLE, PLE, and PSE. After resizing, the large patch is divided into small patches and these small patches are converted to a sequence of patch embeddings by flattening and linear embedding. A class embedding is concatenated to the patch embedding, and the positional embedding is added to the resulting embeddings described above. Then, the obtained embedding is fed into the transformer encoder blocks to generate the final representation. Finally, the learnable class embedding is fed to a softmax layer to classify the emphysema. Main results: To overcome the lack of massive data, the transformer encoder blocks (pre-trained on ImageNet) are transferred and fine-tuned in our ViT model. The average accuracy of the pre-trained ViT model achieves 95.95% in our lab’s own dataset which is higher than that of AlexNet, Inception-V3, MobileNet-V2, ResNet34, and ResNet50. Meanwhile, the pre-trained ViT model outperforms the ViT model without the pre-training. The accuracy of our pre-trained ViT model is higher than or comparable to that by available methods for the public dataset. Significance: The results demonstrated that the proposed ViT model can accurately classify the subtypes of emphysema using CT images. The ViT model can help make an effective computer-aided diagnosis of emphysema, and the ViT method can be extended to other medical applications.

scholarly journals Tenascin-C inactivation impacts lung structure and function beyond lung development

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Sandrine Gremlich ◽  
Matthias Roth-Kleiner ◽  
Lucile Equey ◽  
Kleanthis Fytianos ◽  
Johannes C. Schittny ◽  
...  
Keyword(s):  
Lung Development ◽  
Structure And Function ◽  
Tenascin C ◽  
Lung Structure ◽  
And Function

scholarly journals Correlation between diaphragmatic sagittal rotation and pulmonary dysfunction in patients with ankylosing spondylitis accompanied by kyphosis

2019 ◽  
Vol 47 (5) ◽  
pp. 1877-1883 ◽  
Author(s):  
Chao Liu ◽  
Bing Wu ◽  
Yue Guo ◽  
Kai Song ◽  
Xiangyu Tang ◽  
...  
Keyword(s):  
Ankylosing Spondylitis ◽  
Pulmonary Function ◽  
Vital Capacity ◽  
Sagittal Plane ◽  
Pulmonary Function Tests ◽  
Influencing Factor ◽  
Three Dimensional ◽  
Lung Parenchyma ◽  
Pedicle Subtraction Osteotomy ◽  
Pulmonary Dysfunction

Objective This study was performed to investigate the correlation between pulmonary dysfunction patterns and diaphragmatic sagittal rotation in patients with ankylosing spondylitis accompanied by kyphosis. Methods Thirty patients (27 male, 3 female) with kyphotic deformity secondary to ankylosing spondylitis underwent pedicle subtraction osteotomy and were retrospectively reviewed. All patients had undergone preoperative computed tomography with three-dimensional reconstruction, full-length spine radiographs, and pulmonary function tests. The diaphragmatic angle in the median sagittal plane (DA), pulmonary function test results, and radiological parameters were studied. Results Correlation coefficients were used to present the correlation between the DA and pulmonary function and the global kyphosis (GK), respectively. The data analysis presented positive correlations between the DA value and vital capacity (VC), forced vital capacity (FVC), expiratory reserve volume (ERV), inspiratory reserve volume (IRV) and peak expiratory flow (PEF). There was likewise a negative correlation between DA value and the global kyphosis (GK). Additionally, there were further significantly statistical improvements for DA, ERV, IRV, FVC, and VC, PEF, postoperatively. Conclusions Except for the restriction of the chest wall motion and the abnormalities of lung parenchyma, the diaphragmatic sagittal rotation is also an influencing factor of pulmonary dysfunction in patients with ankylosing spondylitis accompanied by kyphosis.

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