scholarly journals Airway Remodeling Factors During Early-Life Rhinovirus Infection and the Effect of Premature Birth

2021 ◽  
Vol 9 ◽  
Author(s):  
Xilei XuChen ◽  
Jered Weinstock ◽  
Maria Arroyo ◽  
Kyle Salka ◽  
Elizabeth Chorvinsky ◽  
...  
Keyword(s):  
Growth Factors ◽  
Young Children ◽  
Airway Remodeling ◽  
Term Infants ◽  
Matrix Deposition ◽  
Enhanced Production ◽  
Airway Secretion ◽  
Extracellular Matrix Deposition ◽  
Angiopoietin 2 ◽  
Tgf Β1

Background: Early rhinovirus (RV) infection is a strong risk factor for asthma development. Airway remodeling factors play a key role in the progression of the asthmatic condition. We hypothesized that RV infection in young children elicits the secretion of growth factors implicated in airway remodeling and asthma progression.Methods: We examined the nasal airway production of remodeling factors in children ( ≤ 2 years old) hospitalized due to PCR-confirmed RV infection. Airway remodeling proteins included: MMP-1, MMP-2, MMP-7, MMP-9, MMP-10, TIMP-1, TIMP-2, EGF, Angiopoietin-2, G-CSF, BMP-9, Endoglin, Endothelin-1, Leptin, FGF-1, Follistatin, HGF, HB-EGF, PLGF, VEGF-A, VEGF-C, VEGF-D, FGF-2, TGF-β1, TGF-β2, TGF-β3, PDGF AA, PDGF BB, SPARC, Periostin, OPN, and TGF-α.Results: A total of 43 young children comprising RV cases (n = 26) and uninfected controls (n = 17) were included. Early RV infection was linked to (1) enhanced production of several remodeling factors (e.g., HGF, TGFα), (2) lower MMP-9/TIMP-2 and MMP-2/TIMP-2 ratios, and (3) increased MMP-10/TIMP-1 ratios. We also found that relative to term infants, severely premature children had reduced MMP-9/TIMP-2 ratios at baseline.Conclusion: RV infection in young children elicits the airway secretion of growth factors implicated in angiogenesis, fibrosis, and extracellular matrix deposition. Our results highlight the potential of investigating virus-induced airway remodeling growth factors during early infancy to monitor and potentially prevent chronic progression of respiratory disorders in all ages.

scholarly journals Targeting extracellular matrix remodeling in disease: Could resveratrol be a potential candidate?

2016 ◽  
Vol 242 (4) ◽  
pp. 374-383 ◽  
Author(s):  
Renu Agarwal ◽  
Puneet Agarwal
Keyword(s):  
Extracellular Matrix ◽  
Transcription Factors ◽  
Growth Factors ◽  
Molecular Targets ◽  
Mitogen Activated Protein Kinase ◽  
Extracellular Matrix Remodeling ◽  
Matrix Remodeling ◽  
Matrix Deposition ◽  
Mitogen Activated Protein ◽  
Extracellular Matrix Deposition

Disturbances of extracellular matrix homeostasis are associated with a number of pathological conditions. The ability of extracellular matrix to provide contextual information and hence control the individual or collective cellular behavior is increasingly being recognized. Hence, newer therapeutic approaches targeting extracellular matrix remodeling are widely investigated. We reviewed the current literature showing the effects of resveratrol on various aspects of extracellular matrix remodeling. This review presents a summary of the effects of resveratrol on extracellular matrix deposition and breakdown. Mechanisms of action of resveratrol in extracellular matrix deposition involving growth factors and their signaling pathways are discussed. Involvement of phosphoinositol-3-kinase/Akt and mitogen-activated protein kinase pathways and role of transcription factors and sirtuins on the effects of resveratrol on extracellular matrix homeostasis are summarized. It is evident from the literature presented in this review that resveratrol has significant effects on both the synthesis and breakdown of extracellular matrix. The major molecular targets of the action of resveratrol are growth factors and their signaling pathways, phosphoinositol-3-kinase/Akt and mitogen-activated protein kinase pathways, transcription factors, and SIRT-1. The effects of resveratrol on extracellular matrix and the molecular targets appear to be related to experimental models, experimental environment as well as the doses.

Latent adenoviral infection induces production of growth factors relevant to airway remodeling in COPD

2004 ◽  
Vol 286 (1) ◽  
pp. L189-L197 ◽  
Author(s):  
Emiko Ogawa ◽  
W. Mark Elliott ◽  
Fiona Hughes ◽  
Thomas J. Eichholtz ◽  
James C. Hogg ◽  
...  
Keyword(s):  
Growth Factors ◽  
Growth Factor ◽  
Transforming Growth Factor ◽  
Airway Remodeling ◽  
Smooth Muscle Actin ◽  
Tissue Growth ◽  
Chronic Obstructive ◽  
Adenoviral Infection ◽  
E1a Gene ◽  
Tgf Β1

Previous studies showed an association between latent adenoviral infection with expression of the adenoviral E1A gene and chronic obstructive pulmonary disease (COPD). The present study focuses on how the adenoviral E1A gene could alter expression of growth factors by human bronchial epithelial (HBE) cells. The data show that connective tissue growth factor (CTGF) and transforming growth factor (TGF)-β1 mRNA and protein expression were upregulated in E1A-positive HBE cells. Upregulation of CTGF in this in vitro model was independent of TGF-β secreted into the growth medium. Comparison of E1A-positive with E1A-negative HBE cells showed that both expressed cytokeratin but only E1A-positive cells expressed the mesenchymal markers vimentin and α-smooth muscle actin. We conclude that latent infection of epithelial cells by adenovirus E1A could contribute to airway remodeling in COPD by the viral E1A gene, inducing TGF-β1 and CTGF expression and shifting cells to a more mesenchymal phenotype.

scholarly journals TGF-β-Induced α-SMA Expression is Mediated by C/EBPβ Acetylation in Human Alveolar Epithelial Cells In Vitro

2020 ◽  
Author(s):  
Hui Ding ◽  
Jinjun Chen ◽  
Jingping Qin ◽  
Ruhua Chen ◽  
Zili Yi
Keyword(s):  
A549 Cells ◽  
Alveolar Epithelial Cells ◽  
Collagen I ◽  
Alveolar Epithelial ◽  
Matrix Deposition ◽  
Extracellular Matrix Deposition ◽  
Vitro Model ◽  
Relationship Of ◽  
Tgf Β1

Abstract This study sought to determine whether binding of acetylated C/EBPβ to α-SMA promoter could affect its activity and was essential for EMT and extracellular matrix deposition in IPF using in vitro model. The expression of EMT and C/EBPβ in A549 cells with TGF-β as pulmonary fibrotic model were detected by western blotting and qPCR. Collagen-I expression using ELISA was performed. The luciferase activity was used to examine the activity of C/EBPβ. Knockdown of C/EBPβ was performed by siRNA. We also investigated the effect of deacetylation of C/EBPβ on EMT using SIRT1. The binding ability of C/EBPβ with α-SMA promoter was affirmed via ChIP and EMSA. The relationship of α-SMA and acetylated C/EBPβ was investigated by Co-IP. SiRNA-mediated knockdown of C/EBPβ in A549 cells attenuated TGF-β1-induced myofibroblast differentiation and ECM deposition. The extent of association between acetylated C/EBPβ and α-SMA promoter was dynamically monitored. It was confirmed that deacetylation of C/EBPβ in A549 cells successfully ameliorated TGF-β1-induced EMT, as shown by reduction in α-SMA expression and excessive collagen-I accumulation. The EMT and fibrotic effect of TGF-β1 dependent on acetylated C/EBPβ-mediated regulation of α-SMA gene activity. C/EBPβ acetylation may play a central role in pulmonary fibrosis.

scholarly journals TGF-β-induced α-SMA expression is mediated by C/EBPβ acetylation in human alveolar epithelial cells in vitro

2020 ◽  
Author(s):  
Hui Ding ◽  
Jinjun Chen ◽  
Jingping Qin ◽  
Ruhua Chen ◽  
Zili Yi
Keyword(s):  
A549 Cells ◽  
Alveolar Epithelial Cells ◽  
Collagen I ◽  
Alveolar Epithelial ◽  
Matrix Deposition ◽  
Luciferase Activity Assay ◽  
Extracellular Matrix Deposition ◽  
Vitro Model ◽  
Tgf Β1

Abstract Background This study sought to determine whether binding of acetylated C/EBPβ to α-SMA promoter could affect its activity and was essential for EMT and extracellular matrix deposition in IPF using in vitro model. Methods Through western blotting, the expression of EMT and C/EBPβ were detected in A549 cells with TGF-β as pulmonary fibrotic model in vitro. Moreover, the expression of C/EBPβ mRNA via Real Time-PCR and Collagen-I expression using ELISA were performed. The luciferase activity assay was used to examine the activity of C/EBPβ. The knockdown expression of C/EBPβ gene was prepared in A549 cells with C/EBPβ siRNA. We also investigated the effect of deacetylation of C/EBPβ on EMT using SIRT1. The binding ability of C/EBPβ with the α-SMA promoter was affirmed via ChIP and EMSA. Furthermore, the relationship between α-SMA and acetylated C/EBPβ was investigated using the co-immunoprecipitation. Results SiRNA-mediated knockdown of C/EBPβ in A549 cells attenuated TGF-β1-induced myofibroblast differentiation and ECM deposition. The extent of association between acetylated C/EBPβ and the α-SMA promoter was dynamically monitored. Furthermore, it was confirmed that deacetylation of C/EBPβ in A549 cells successfully ameliorated TGF-β1-induced EMT, as shown by reduction in α-SMA expression and excessive collagen-I accumulation. Conclusions Collectively, our data suggested that the EMT and fibrotic effect of TGF-β1 could be dependent on acetylated C/EBPβ-mediated regulation of α-SMA gene activity. This thus suggests that C/EBPβ acetylation may play a central role in pulmonary fibrosis.

scholarly journals The molecular basis of hypertrophic scars

2016 ◽  
Vol 4 ◽  
pp. 1-12 ◽  
Author(s):  
Zhensen Zhu ◽  
Jie Ding ◽  
Edward E. Tredget
Keyword(s):  
Extracellular Matrix ◽  
Wound Healing ◽  
Growth Factors ◽  
Molecular Basis ◽  
Hypertrophic Scars ◽  
Deep Dermis ◽  
Matrix Deposition ◽  
Prevention And Treatment ◽  
Extracellular Matrix Deposition ◽  
Current Advance

Abstract Hypertrophic scars (HTS) are caused by dermal injuries such as trauma and burns to the deep dermis, which are red, raised, itchy and painful. They can cause cosmetic disfigurement or contractures if craniofacial areas or mobile region of the skin are affected. Abnormal wound healing with more extracellular matrix deposition than degradation will result in HTS formation. This review will introduce the physiology of wound healing, dermal HTS formation, treatment and difference with keloids in the skin, and it also review the current advance of molecular basis of HTS including the involvement of cytokines, growth factors, and macrophages via chemokine pathway, to bring insights for future prevention and treatment of HTS.

scholarly journals Aminoguanidine Ameliorates Overexpression of Prosclerotic Growth Factors and Collagen Deposition in Experimental Diabetic Nephropathy

2001 ◽  
Vol 12 (10) ◽  
pp. 2098-2107 ◽  
Author(s):  
DARREN J. KELLY ◽  
RICHARD E. GILBERT ◽  
ALISON J. COX ◽  
TINA SOULIS ◽  
GEORGE JERUMS ◽  
...  
Keyword(s):  
Diabetic Nephropathy ◽  
Growth Factors ◽  
Growth Factor ◽  
Experimental Diabetes ◽  
Fold Increase ◽  
Diabetic Rats ◽  
Renal Tubules ◽  
Collagen Deposition ◽  
Matrix Deposition ◽  
Tgf Β1

Abstract. Profibrotic cytokines and the formation of advanced-glycation end products (AGE) have both been implicated in the pathogenesis of glomerulosclerosis in diabetic kidney disease. However, tubulointerstitial pathology is also an important determinant of progressive renal dysfunction in diabetic nephropathy. This study sought to investigate the expression of profibrotic growth factors and matrix deposition in the glomerulus and the tubulointerstitium and to examine the effect of blocking AGE formation in experimental diabetic nephropathy. Thirty-six male Sprague-Dawley rats were randomized into control and diabetic groups. Diabetes was induced in 24 rats by streptozotocin. Twelve diabetic rats were further randomized to receive the inhibitor of AGE formation, aminoguanidine (1 g/l drinking water). At 6 mo, experimental diabetes was associated with a three-fold increase in expression of transforming growth factor (TGF)-β1 (P< 0.01versuscontrol) and five-fold increase in platelet-derived growth factor (PDGF)-B gene expression (P< 0.01versuscontrol) in the tubulointerstitium.In situhybridization demonstrated a diffuse increase in both TGF-β1 and PDGF-B mRNA in renal tubules. Aminoguanidine attenuated not only the overexpression of TGF-β1 and PDGF-B but also reduced type IV collagen deposition in diabetic rats (P< 0.05). TGF-β1 and PDGF mRNA within glomeruli were also similarly increased with diabetes and attenuated with aminoguanidine. The observed beneficial effects of aminoguanidine on the tubulointerstitium in experimental diabetes suggest that AGE-mediated expression of profibrotic cytokines may contribute to tubulointerstitial injury and the pathogenesis of diabetic nephropathy.

Sign in / Sign up

Export Citation Format

Share Document