A5053173891- Muscle Physiology and Disorders
- Proteoglycans and glycosaminoglycans research
- Connective Tissue Growth Factor Research
- Connective tissue disorders research
- Protease and Inhibitor Mechanisms
- Cell Adhesion Molecules Research
- TGF-β signaling in diseases
- Muscle metabolism and nutrition
- Periodontal Regeneration and Treatments
- Mesenchymal stem cell research
- Fibroblast Growth Factor Research
- Glycosylation and Glycoproteins Research
- Cholinesterase and Neurodegenerative Diseases
- Genetics and Physical Performance
- Adipose Tissue and Metabolism
- Tendon Structure and Treatment
- Systemic Sclerosis and Related Diseases
- Marine Biology and Environmental Chemistry
- Hippo pathway signaling and YAP/TAZ
- Osteoarthritis Treatment and Mechanisms
- Cellular Mechanics and Interactions
- Environmental Toxicology and Ecotoxicology
- Exercise and Physiological Responses
- Liver Disease Diagnosis and Treatment
- Tissue Engineering and Regenerative Medicine
San Sebastián University
2023-2025
Fundación Ciencia and Vida
2020-2025
Pontificia Universidad Católica de Chile
2015-2024
Fundación Chile
2018-2022
Universidad de Magallanes
2017
University of Chile
1980-2014
Universidad Bernardo O'Higgins
2014
Park University
2006-2011
Institut Agro Dijon
2010
Universidad Andrés Bello
2007-2008
Skeletal muscle fibrosis is strongly associated with the differentiation of its resident multipotent fibro/adipogenic progenitors (FAPs) towards myofibroblast phenotype. Although TGF-β signaling well-known for driving FAPs and fibrosis, due to pleiotropic functions complete inhibition not suitable treating fibrotic disorders such as muscular dystrophies. Here, we describe that operates through mechanosensitive transcriptional regulators YAP/TAZ determine fate skeletal fibrosis. Spatial...
Heparan sulfate and heparin, two sulfated glycosaminoglycans (GAGs), extracted collagen-tailed acetylcholinesterase (AChE) from the extracellular matrix (ECM) of electric organ Discopyge tschudii. The effect heparan heparin was abolished by protamine; other GAGs could not extract esterase. solubilization asymmetric AChE apparently occurs through formation a soluble AChE-GAG complex 30S. Heparitinase treatment but chondroitinase ABC ECM released forms. This provides direct evidence for vivo...
Duchenne muscular dystrophy (DMD) is the most common inherited neuromuscular disease, and characterized by lack of dystrophin, muscle wasting, increased transforming growth factor (TGF)-β Smad-dependent signalling fibrosis. Acting via Mas receptor, angiotensin-1-7 [Ang-(1-7)], part renin–angiotensin system, with opposite effect to that angiotensin II. We hypothesized Ang-(1-7)/Mas receptor axis might protect chronically damaged tissues as in skeletal DMD mouse model mdx. Infusion or oral...
Background/Aim Hypercaloric diet ingestion and sedentary lifestyle result in obesity. Metabolic syndrome is a cluster of clinical features secondary to obesity, considered as pre-diabetic condition recognized an independent risk factor for cardiovascular diseases. To better understand the relationship between metabolic disease well development novel therapeutic strategies, animal models that reproduce etiology, course outcomes these pathologies are required. The aim this work was...
In Duchenne muscular dystrophy (DMD) and the mdx mouse model, absence of cytoskeletal protein dystrophin causes defective anchoring myofibres to basal lamina. The resultant myofibre degeneration necrosis lead a progressive loss muscle mass, increased fibrosis ultimately fatal weakness. Connective tissue growth factor (CTGF/CCN-2) is critically involved in several chronic fibro-degenerative diseases. DMD, role CTGF might extend well beyond replacement secondary fibres, since its...
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease in which upper and lower motoneurons degenerate leading to muscle wasting, paralysis eventually death from respiratory failure. Several studies indicate that skeletal contributes progression; however the molecular mechanisms remain elusive. Fibrosis common feature under chronic damage conditions such as those caused by muscular dystrophies or denervation. However, exact of fibrosis induction cellular bases this...
ABSTRACT Fibro–adipogenic progenitors (FAPs) are tissue-resident mesenchymal stromal cells (MSCs) required for proper skeletal muscle development, regeneration and maintenance. However, FAPs also responsible fibro-fatty scar deposition following chronic damage. We aimed to investigate the role of functional cross-talk between TGF-β PDGFRα signaling pathways in fate FAPs. Here, we show that number correlates with levels extracellular matrix during repair. Interestingly, expression changed...
Transcription of specific skeletal muscle genes requires the expression regulatory factor myogenin. To assess role extracellular matrix (ECM) in differentiation, inhibitors proteoglycan synthesis, sodium chlorate and beta-D-xyloside, were used. Treatment cultured cells with each inhibitor substantially abolished creatine kinase alpha-dystroglycan. This inhibition was totally reversed by addition exogenous ECM. Myoblast treatment affected deposition assembly ECM constituents glypican,...
In diabetic nephropathy, connective tissue growth factor (CTGF) is upregulated and bone morphogenetic protein 7 (BMP-7) downregulated. CTGF known to inhibit BMP-4, but similar cross-talk between BMP-7 has not been studied. this study, it was hypothesized that acts as an inhibitor of signaling activity in nephropathy. Compared with wild-type CTGF(+/+) mice, CTGF(+/-) mice had approximately 50% lower mRNA protein, less severe albuminuria, no thickening the glomerular basement membrane,...
Transforming growth factor-beta (TGF-beta) is a multifunctional cytokine that signals to the nucleus through cell surface transmembrane receptors with serine/threonine kinase activity and cytoplasmic effectors, including Smad proteins. Here we describe two novel modulators of this pathway, lipoprotein-receptor related protein (LRP-1) decorin. Decorin null (Dcn null) myoblasts showed diminished TGF-beta response restored by decorin re-expression. Importantly, reactivation occurs without...
Fibrotic disorders are typified by excessive connective tissue and extracellular matrix (ECM) deposition that precludes normal healing processes of different tissues. Connective growth factor (CTGF) seems to be involved in the fibrotic response. Several muscular dystrophies characterized a progressive weakness wasting musculature, extensive fibrosis. However, exact role CTGF skeletal muscle is unknown. Here we show myoblasts myotubes able synthesize response transforming type-beta (TGF-beta)...
Heparan sulfate proteoglycans (HSPGs) are critical modulators of growth factor activities. Skeletal muscle differentiation is strongly inhibited by fibroblast 2 (FGF-2). We have shown that HSPGs present at the plasma membrane expressed in myoblasts and downregulated during differentiation. An exception glypican-1, which throughout myogenic process. Myoblasts do not express glypican-1 exhibit defective differentiation, with an increase receptor binding FGF-2, concomitant increased signaling....
Fibrotic disorders are the end point of many chronic diseases in different tissues, where an accumulation extracellular matrix occurs, mainly because action connective tissue growth factor (CTGF/CCN2). Little is known about how this activity regulated. We found that decorin null myoblasts more sensitive to CTGF than wild type myoblasts, as evaluated by fibronectin or collagen III. Decorin added exogenously negatively regulated pro-fibrotic and induction actin stress fibers. Using...
Abstract Muscular dystrophies are diseases characterized by muscle weakness together with cycles of degeneration and regeneration fibres, resulting in a progressive decrease mass, diminished force generation an increase fibrosis. Fibrotic disorders the endpoint many chronic different tissues, where accumulation extracellular matrix (ECM) occurs. Connective tissue growth factor CTGF/CCN2, which is over‐expressed muscular dystrophies, plays major role scarring conditions. To test hypothesis...
Fibrosis, an excessive collagen accumulation, results in scar formation, impairing function of vital organs and tissues. Fibrosis is a hallmark muscular dystrophies, including the lethal Duchenne dystrophy (DMD), which remains incurable. Substitution muscle by fibrotic tissue also complicates gene/cell therapies for DMD. Yet, no optimal models to study fibrosis are available. In widely used mdx mouse model DMD, extensive develops diaphragm only at advanced adulthood, about two years age...
Connective tissue growth factor (CTGF/CCN-2) is mainly involved in the induction of extracellular matrix (ECM) proteins. The levels CTGF correlate with degree and severity fibrosis many tissues, including dystrophic skeletal muscle. overexpression tibialis anterior muscle using an adenoviral vector reproduced features observed muscles damage regeneration, fibrotic response decrease strength. renin-angiotensin system genesis progression diseases through its main components angiotensin-II...
Therapy for nonalcoholic steatohepatitis (NASH) is limited. Andrographolide (ANDRO), a botanical compound, has potent anti-inflammatory activity due to its ability inhibit NF-κB. ANDRO been also shown the NLRP3 inflammasome, relevant pathway in NASH. Our aim was evaluate effects of NASH and influence on inflammasome activation this setting. Thus, mice were fed choline-deficient-amino-acid-defined (CDAA) diet with/without concomitant administration (1 mg/kg, 3-times/week). Also, we assessed...
Skeletal muscle atrophy is a pathological condition characterized by the loss of strength and mass, an increase in myosin heavy chain (MHC) degradation expression two muscle-specific ubiquitin ligases: atrogin-1 MuRF-1. Angiotensin II (AngII) induces atrophy. Angiotensin-(1–7) [Ang-(1–7)], through its receptor Mas, produces opposite effects than AngII. We assessed Ang-(1–7) on skeletal induced Our results show that Ang-(1–7), prevents AngII gastrocnemius: decrease fibre diameter, MHC levels...