scholarly journals Determination of the Role of the Distal Outflow Pathway Tissue in Glucocorticoid-induced Ocular Hypertension

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Tyler Margetts ◽  
Michael Peng ◽  
Chenna Kesavulu Sugali ◽  
Naga Pradeep Rayana ◽  
Jiannong Dai ◽  
...  
Keyword(s):  
Ocular Hypertension ◽  
Perfusion Culture ◽  
Pressure Transducers ◽  
Cell Functions ◽  
Matrix Deposition ◽  
3D Printed ◽  
Low Glucose ◽  
Extracellular Matrix Deposition ◽  
Outflow Pathway

Introduction Prolonged application of glucocorticoids (GCs) induces ocular hypertension (OHT) and glaucoma. This increased intraocular pressure (IOP) is due to pathological changes in the trabecular meshwork (TM) outflow pathway tissues including impaired cell functions and extracellular matrix deposition. The changes and role of the TM in GC-induced OHT have been well studied. However, the role of the tissues distal to the TM (distal outflow tissues) is unclear. This study aims to further uncover the role of distal outflow tissue in GC-induced OHT using a novel perfusion organ culture (POC) model. Methods Huma corneal rims tissues were attached to 3D printed transparent perfusion plates using a combination of thin and thick glues. The artificial anterior chamber was perfused with DMEM-low glucose medium at 2ul/min to mimic aqueous humor production, and IOP was recorded using pressure transducers and a computerized system. To determine the role of distal tissue in GC-induced IOP changes, the TM tissue was carefully removed from both eyes, and one eye was treated with ethanol (EtOH) and the fellow eye with dexamethasone (DEX). Results The model was validated through a comparison of the IOP and TM stiffness of glue contaminated to non-contaminated corneal rims. The glue contaminated rim showed highly increased IOP and TM stiffness while the non-contaminated rim showed normal values. After validation, the TM was removed from paired corneal rims. One rim was treated with 100nM DEX and the fellow rim with 0.1% EtOH. The DEX treated rim showed increase in IOP while the EtOH control showed little change. Conclusion We created a novel corneal rim perfusion culture model for the study of GC-induced OHT. This model showed promising results of distal outflow involvement in glucocorticoid induced ocular hypertension. Further studies are needed to elucidate the role of distal outflow tissues in GC responsiveness in the eye.

scholarly journals Role of Nampt-Sirt6 Axis in Renal Proximal Tubules in Extracellular Matrix Deposition in Diabetic Nephropathy

Cell Reports ◽  
2019 ◽  
Vol 27 (1) ◽  
pp. 199-212.e5 ◽  
Author(s):  
Hirokazu Muraoka ◽  
Kazuhiro Hasegawa ◽  
Yusuke Sakamaki ◽  
Hitoshi Minakuchi ◽  
Takahisa Kawaguchi ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Diabetic Nephropathy ◽  
Proximal Tubules ◽  
Renal Proximal Tubules ◽  
Matrix Deposition ◽  
Extracellular Matrix Deposition

scholarly journals Autocrine regulation of biliary pathology by activated cholangiocytes

2012 ◽  
Vol 302 (5) ◽  
pp. G473-G483 ◽  
Author(s):  
Kendal Jensen ◽  
Marco Marzioni ◽  
Kamruzzaman Munshi ◽  
Syeda Afroze ◽  
Gianfranco Alpini ◽  
...  
Keyword(s):  
Cholestatic Liver Disease ◽  
Autocrine Factors ◽  
Matrix Deposition ◽  
Toxic Injury ◽  
Biliary Pathology ◽  
Extracellular Matrix Deposition ◽  
And Function ◽  
Subsequent Modification ◽  
Made In

The bile duct system of the liver is lined by epithelial cells (i.e., cholangiocytes) that respond to a large number of neuroendocrine factors through alterations in their proliferative activities and the subsequent modification of the microenvironment. As such, activation of biliary proliferation compensates for the loss of cholangiocytes due to apoptosis and slows the progression of toxic injury and cholestasis. Over the course of the last three decades, much progress has been made in identifying the factors that trigger the biliary epithelium to remodel and grow. Because a large number of autocrine factors have recently been identified as relevant clinical targets, a compiled review of their contributions and function in cholestatic liver diseases would be beneficial. In this context, it is important to define the specific processes triggered by autocrine factors that promote cholangiocytes to proliferate, activate neighboring cells, and ultimately lead to extracellular matrix deposition. In this review, we discuss the role of each of the known autocrine factors with particular emphasis on proliferation and fibrogenesis. Because many of these molecules interact with one another throughout the progression of liver fibrosis, a model speculating their involvement in the progression of cholestatic liver disease is also presented.

p75NTR silencing inhibits proliferation, migration and extracellular matrix deposition of hypertrophic scar fibroblasts by activating autophagy through inhibiting PI3K/Akt/mTOR pathway

2020 ◽  
Author(s):  
Wen Shi ◽  
Yan Wu ◽  
Donghui Bian
Keyword(s):  
Extracellular Matrix ◽  
Wound Healing ◽  
Hypertrophic Scar ◽  
Mtor Pathway ◽  
Neurotrophin Receptor ◽  
P75 Neurotrophin Receptor ◽  
Inhibitory Effects ◽  
Matrix Deposition ◽  
Extracellular Matrix Deposition

Hypertrophic scar (HS) results from abnormal wound healing, accompanied by excessive hypercellularity, migration and extracellular matrix (ECM) deposition. Autophagy dysregulation plays crucial roles during HS formation. The overexpressed p75 neurotrophin receptor (p75NTR) in injured skin tissue after wound healing becomes a factor aggravating scar. The study was designed to investigate the role of p75NTR and p75NTR-mediated autophagy in the process of HS. The results revealed that p75NTR expression was significantly upregulated while that of autophagy proteins was downregulated in cicatrix at 3 and 6 months after burn, which was recovered at 12 months. p75NTR silencing inhibited proliferation, migration and ECM deposition of hypertrophic scar fibroblasts (HSF), whereas p75NTR overexpression presented the opposite results. Silencing of p75NTR reduced the expression of PI3K/Akt/mTOR signaling molecules while enhanced that of autophagy proteins. Importantly, PI3K agonist (IGF-1) intervention notably decreased the levels of LC3B II/I and Beclin-1, and restored the inhibitory effects of p75NTR silencing on proliferation, migration and ECM deposition of HSF. Concurrently, autophagy inhibitor 3-methyladenine (3-MA) treatment exhibited the same variation trends with IGF-1. Taken together, these findings demonstrated that p75NTR silencing inhibits proliferation, migration and ECM deposition of HSF by activating autophagy through inhibiting PI3K/Akt/mTOR pathway.

scholarly journals HHV-6A Infection and Systemic Sclerosis: Clues of a Possible Association

2019 ◽  
Vol 8 (1) ◽  
pp. 39
Author(s):  
Elisabetta Caselli ◽  
Irene Soffritti ◽  
Maria D’Accolti ◽  
Daria Bortolotti ◽  
Roberta Rizzo ◽  
...  
Keyword(s):  
Systemic Sclerosis ◽  
Plasma Levels ◽  
Human Herpesvirus ◽  
Infectious Agents ◽  
Internal Organs ◽  
Matrix Deposition ◽  
Skin Biopsies ◽  
Extracellular Matrix Deposition

Systemic sclerosis (SSc) is an autoimmune disease characterized by vasculopathy, excessive extracellular matrix deposition, and fibrosis of the skin and internal organs. Several infectious agents, including human herpesvirus-6 (HHV-6), have been suggested as possible triggering factors, but a direct association is still missing. We characterized 26 SSc patients for the presence of HHV-6 in tissues and blood, the anti-HHV-6 response, HLA-G plasma levels, and KIR typing. Given the prominent role of endothelial cells (EC) in SSc pathogenesis, along with HHV-6 tropism for EC, we also investigated the expression of pro-fibrosis factors in HHV-6 infected EC. Results showed the presence of HHV-6A in skin biopsies, and an increased virus load was associated with disease severity and poor natural killer (NK) response against the virus, particularly in subjects exhibiting a KIR2 phenotype. HLA-G plasma levels were significantly higher in HHV-6A/B-KIR2 positive SSc patients and in vitro HHV-6A infection-induced pro-fibrosis factors expression in EC, supporting its role in the development of the fibrosing process. Our data suggest an association between virus infection/reactivation and disease, opening the way to future studies to understand the mechanisms by which HHV-6A might contribute to the multifactorial pathogenesis of SSc.

scholarly journals Liver Fibrosis and Mechanisms of the Protective Action of Medicinal Plants Targeting Inflammation and the Immune Response

2015 ◽  
Vol 2015 ◽  
pp. 1-14 ◽  
Author(s):  
Florent Duval ◽  
Jorge E. Moreno-Cuevas ◽  
María Teresa González-Garza ◽  
Carmen Maldonado-Bernal ◽  
Delia Elva Cruz-Vega
Keyword(s):  
Immune Response ◽  
Liver Fibrosis ◽  
Medicinal Plants ◽  
Protective Action ◽  
Inflammatory Cells ◽  
Central Feature ◽  
Matrix Deposition ◽  
High Incidence ◽  
Extracellular Matrix Deposition

Inflammation is a central feature of liver fibrosis as suggested by its role in the activation of hepatic stellate cells leading to extracellular matrix deposition. During liver injury, inflammatory cells are recruited in the injurious site through chemokines attraction. Thus, inflammation could be a target to reduce liver fibrosis. The pandemic trend of obesity, combined with the high incidence of alcohol intake and viral hepatitis infections, highlights the urgent need to find accessible antifibrotic therapies. Medicinal plants are achieving popularity as antifibrotic agents, supported by their safety, cost-effectiveness, and versatility. The aim of this review is to describe the role of inflammation and the immune response in the pathogenesis of liver fibrosis and detail the mechanisms of inhibition of both events by medicinal plants in order to reduce liver fibrosis.

scholarly journals The Role of Hypoxia in Corneal Extracellular Matrix Deposition and Cell Motility

2019 ◽  
Vol 303 (6) ◽  
pp. 1703-1716 ◽  
Author(s):  
Obianamma E. Onochie ◽  
Anwuli J. Onyejose ◽  
Celeste B. Rich ◽  
Vickery Trinkaus‐Randall
Keyword(s):  
Extracellular Matrix ◽  
Cell Motility ◽  
Matrix Deposition ◽  
Extracellular Matrix Deposition

scholarly journals Laminin α4 contributes to airway remodeling and inflammation in asthma

2019 ◽  
Vol 317 (6) ◽  
pp. L768-L777 ◽  
Author(s):  
Pavan Prabhala ◽  
David B. Wright ◽  
Patricia Robbe ◽  
Catrin Bitter ◽  
Tonio Pera ◽  
...  
Keyword(s):  
Lung Function ◽  
Airway Remodeling ◽  
Cell Phenotype ◽  
Asthmatic Patients ◽  
Matrix Deposition ◽  
Extracellular Matrix Deposition ◽  
Characteristic Features ◽  
Blocking Antibodies

Airway inflammation and remodeling are characteristic features of asthma, with both contributing to airway hyperresponsiveness (AHR) and lung function limitation. Airway smooth muscle (ASM) accumulation and extracellular matrix deposition are characteristic features of airway remodeling, which may contribute to persistent AHR. Laminins containing the α2-chain contribute to characteristics of ASM remodeling in vitro and AHR in animal models of asthma. The role of other laminin chains, including the laminin α4 and α5 chains, which contribute to leukocyte migration in other diseases, is currently unknown. The aim of the current study was to investigate the role of these laminin chains in ASM function and in AHR, remodeling, and inflammation in asthma. Expression of both laminin α4 and α5 was observed in the human and mouse ASM bundle. In vitro, laminin α4 was found to promote a pro-proliferative, pro-contractile, and pro-fibrotic ASM cell phenotype. In line with this, treatment with laminin α4 and α5 function-blocking antibodies reduced allergen-induced increases in ASM mass in a mouse model of allergen-induced asthma. Moreover, eosinophilic inflammation was reduced by the laminin α4 function-blocking antibody as well. Using airway biopsies from healthy subjects and asthmatic patients, we found inverse correlations between ASM α4-chain expression and lung function and AHR, whereas eosinophil numbers correlated positively with expression of laminin α4 in the ASM bundle. This study, for the first time, indicates a prominent role for laminin α4 in ASM function and in inflammation, AHR, and remodeling in asthma, whereas the role of laminin α5 is more subtle.

scholarly journals Characterization of the role of Activator Protein 1 signaling pathway on extracellular matrix deposition in uterine leiomyoma

F&S Science ◽  
2020 ◽  
Vol 1 (1) ◽  
pp. 78-89
Author(s):  
Justin Pilgrim ◽  
Jacquel Arismendi ◽  
Anthony DeAngelis ◽  
Terrence Lewis ◽  
Joy Britten ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Signaling Pathway ◽  
Uterine Leiomyoma ◽  
Activator Protein 1 ◽  
Matrix Deposition ◽  
Activator Protein ◽  
Extracellular Matrix Deposition
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