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Gene Dec 2021Skeletal muscle is one of the most important economic traits in the poultry industry whose development goes through several processes influenced by several candidate...
Skeletal muscle is one of the most important economic traits in the poultry industry whose development goes through several processes influenced by several candidate genes. This study explored the regulatory role of DCN on MSTN and the influence of these genes on the proliferation and differentiation of embryonic myoblasts in Leizhou black ducks. Embryonic myoblasts were transfected with over-expressing DCN, Si-DCN, and empty vector and cultured for 24 h, 48 h, and 72 h of proliferation and the comparative expression of DCN and MSTN were measured. The results showed that cells transfected with the over-expression DCN had a significantly (P < 0.05) higher expression of DCN mRNA than the normal group and the expression of MSTN mRNA showed a downward trend during the proliferation of myoblasts. DCN mRNA expression was lower in cells transfected with Si-DCN than the normal group in all stages of proliferation. While the expression of MSTN in the Si-DCN transfected group was higher than the normal group with a significant (P < 0.05) difference at the 72 h stage. DCN mRNA increased at the early stage of differentiation but decreased (P > 0.05) from the 6th day to the 8th day of differentiation. The level of MSTN increased gradually during the differentiation process of myoblasts until it decreased significantly on the 8th day. These results show that DCN enhances the proliferation and differentiation of Leizhou black duck myoblasts and suppresses MSTN activity.
Topics: Animals; Avian Proteins; Cell Differentiation; Cell Proliferation; Decorin; Ducks; Muscle, Skeletal; Myoblasts; Myostatin; Poultry; RNA, Messenger
PubMed: 34364913
DOI: 10.1016/j.gene.2021.145884 -
European Journal of Endocrinology Feb 2018Growth hormone (GH) stimulates connective tissue and muscle growth, an effect that is potentiated by testosterone. Decorin, a myokine and a connective tissue protein,... (Randomized Controlled Trial)
Randomized Controlled Trial
CONTEXT
Growth hormone (GH) stimulates connective tissue and muscle growth, an effect that is potentiated by testosterone. Decorin, a myokine and a connective tissue protein, stimulates connective tissue accretion and muscle hypertrophy. Whether GH and testosterone regulate decorin in humans is not known.
OBJECTIVE
To determine whether decorin is stimulated by GH and testosterone.
DESIGN
Randomized, placebo-controlled, double-blind study.
PARTICIPANTS AND INTERVENTION
96 recreationally trained athletes (63 men, 33 women) received 8 weeks of treatment followed by a 6-week washout period. Men received placebo, GH (2 mg/day), testosterone (250 mg/week) or combination. Women received either placebo or GH (2 mg/day).
MAIN OUTCOME MEASURE
Serum decorin concentration.
RESULTS
GH treatment significantly increased mean serum decorin concentration by 12.7 ± 4.2%; < 0.01. There was a gender difference in the decorin response to GH, with greater increase in men than in women (∆ 16.5 ± 5.3%; < 0.05 compared to ∆ 9.4 ± 6.5%; = 0.16). Testosterone did not significantly change serum decorin. Combined GH and testosterone treatment increased mean decorin concentration by 19.5 ± 3.7% ( < 0.05), a change not significantly different from GH alone.
CONCLUSION
GH significantly increases circulating decorin, an effect greater in men than in women. Decorin is not affected by testosterone. We conclude that GH positively regulates decorin in humans in a gender-dimorphic manner.
Topics: Adult; Androgens; Athletes; Decorin; Double-Blind Method; Female; Human Growth Hormone; Humans; Male; Sex Factors; Testosterone; Young Adult
PubMed: 29138241
DOI: 10.1530/EJE-17-0844 -
Current Opinion in Rheumatology Nov 2016This article updates on the concept that muscle-derived cytokines (myokines) play important roles in muscle health and disease. (Review)
Review
PURPOSE OF REVIEW
This article updates on the concept that muscle-derived cytokines (myokines) play important roles in muscle health and disease.
RECENT FINDINGS
Interleukin-6 (IL-6) is released from normal skeletal muscle in response to exercise, mediating both anti-inflammatory responses and metabolic adaptations, actions contradictory to the prevailing view that IL-6 is a proinflammatory cytokine that is inducing and propagating disease. The anti-inflammatory effects of IL-6 result from its trans-membrane signalling capability, via membrane-bound receptors, whereas its proinflammatory effects result instead from signalling via the soluble IL-6 receptor and gp130. IL-15 is elevated following exercise, promoting muscle fibre hypertrophy in some circumstances, while inducing fibre apoptosis in others. This functional divergence appears because of variations in expression of IL-15 receptor isoforms. Decorin, a recently described myokine, is also elevated following exercise in normal muscle, and promotes muscle fibre hypertrophy by competitively binding to, and thus inhibiting, myostatin, a negative regulator of muscle protein synthesis. Exercise-induced myostatin downregulation thus promotes muscle fibre growth, prompting recent trials of a biological myostatin inhibitor in inclusion body myositis.
SUMMARY
Myokines appear to exert diverse beneficial effects, though their mechanistic roles in myositis and other myopathologies remain poorly understood.
Topics: Cytokines; Decorin; Exercise; Humans; Interleukin-6; Muscle Fibers, Skeletal; Muscle, Skeletal; Muscular Diseases; Myostatin; Receptors, Interleukin-6; Signal Transduction
PubMed: 27548653
DOI: 10.1097/BOR.0000000000000337 -
The Indian Journal of Medical Research Apr 2021Decorin is a proteoglycan that plays a role in the binding of collagen and has an important role in the pathogenesis of osteoarthritis (OA). This study was aimed to...
BACKGROUND & OBJECTIVES
Decorin is a proteoglycan that plays a role in the binding of collagen and has an important role in the pathogenesis of osteoarthritis (OA). This study was aimed to determine serum and synovial fluid decorin levels in patients with knee OA and to investigate whether these levels were associated with OA and the Western Ontario and McMaster Universities Osteoarthritis (WOMAC) score.
METHODS
In this prospective study 88 participants were included (44 knee OA and 44 with other knee joint diseases) in the study and control groups. Knee function was assessed using the WOMAC score. The serum and synovial fluid decorin levels were analyzed using a human decorin ELISA. Binary logistic regression with a single and multi-categorical predictor was used to determine the possible risk factors for OA.
RESULTS
The serum decorin levels were significantly higher in the OA group than the control group (P<0.002).s The synovial fluid decorin levels were not significantly different between OA and control groups. WOMAC score [odds ratio (OR)=1.073, 95% confidence interval (CI): 1.032-1.116, P<0.001] and high serum decorin levels (OR=1.114, 95%CI: 1.030-1.205, P=0.007) were found to be significant in the determination of OA. Serum decorin levels were positively correlated with the WOMAC score in OA.
INTERPRETATION & CONCLUSIONS
An increased serum decorin levels may be indicative of changes in extracellular matrix structure. The positive correlation between serum decorin level and WOMAC score supports this result. Increased serum decorin levels and WOMAC score were found to be risk factors associated with OA. However, the decorin level in the joint fluid was not associated with OA.
Topics: Decorin; Humans; Osteoarthritis, Knee; Prospective Studies; Severity of Illness Index; Synovial Fluid
PubMed: 34380791
DOI: 10.4103/ijmr.IJMR_2020_18 -
Frontiers in Oncology 2021Decorin exhibits inhibitory effects in tumorigenesis in various types of cancers. The clinical characteristics of 42 patients with GBM were reviewed and analyzed....
Decorin exhibits inhibitory effects in tumorigenesis in various types of cancers. The clinical characteristics of 42 patients with GBM were reviewed and analyzed. Lentiviral constructs for decorin overexpression and shRNA-mediated silencing were established for U87MG cells and T98G cells, respectively. The expressions of EMT- and autophagy-associated markers were detected in GBM cell lines. The migration and invasion of the glioma cells were assayed to reflect the malignant behavior of GBM. A mouse xenograft model was used to verify the effect of decorin on autophagy . Reduced expression of decorin in glioma tissues was associated with a poor survival of the patients. Decorin overexpression suppressed cell migration, invasion and attenuated EMT phenotype in glioma cell lines. Further study indicated that decorin inhibited EMT phenotype through the induction of autophagy. The mechanisms include inhibiting the activation of c-Met/Akt/mTOR signaling and regulating the expressions of mesenchymal markers including Slug, vimentin and Twist, and epithelial marker E-cadherin. In addition, decorin overexpression in a mice model can also suppress the GBM invasion and EMT phenotype. In conclusion, decorin suppresses invasion and EMT phenotype of glioma by inducing autophagy c-Met/Akt/mTOR axis.
PubMed: 34386415
DOI: 10.3389/fonc.2021.659353 -
Taiwanese Journal of Obstetrics &... Jun 2018
Topics: Decorin; Female; Humans; Infant, Newborn; Infant, Premature; Pregnancy; Premature Birth
PubMed: 29880190
DOI: 10.1016/j.tjog.2018.04.029 -
Journal of Biomechanical Engineering Jun 2022Cervical remodeling is critical for a healthy pregnancy. The proper regulation of extracellular matrix (ECM) turnover leads to remodeling throughout gestation,...
Cervical remodeling is critical for a healthy pregnancy. The proper regulation of extracellular matrix (ECM) turnover leads to remodeling throughout gestation, transforming the tissue from a stiff material to a compliant, extensible, viscoelastic tissue prepared for delivery. Small leucine-rich proteoglycans (SLRPs) regulate structural fiber assembly in the cervical ECM and overall tissue material properties. To quantify the SLRPs' mechanical role in the cervix, whole cervix specimens from nonpregnant and late pregnant knockout mice of SLRPs, decorin and biglycan, were subjected to cyclic load-unload, ramp-hold, and load-to-failure mechanical tests. Further, a fiber composite material model, accounting for collagen fiber bundle waviness, was developed to describe the cervix's three-dimensional large deformation equilibrium behavior. In nonpregnant tissue, SLRP knockout cervices have the same equilibrium material properties as wild-type tissue. In contrast, the load-to-failure and ramp-hold tests reveal SLRPs impact rupture and time-dependent relaxation behavior. Loss of decorin in nonpregnant (NP) cervices results in inferior rupture properties. After extensive remodeling, cervical strength is similar between all genotypes, but the SLRP-deficient tissue has a diminished ability to dissipate stress during a ramp-hold. In mice with a combined loss of decorin and biglycan, the pregnant cervix loses its extensibility, compliance, and viscoelasticity. These results suggest that decorin and biglycan are necessary for crucial extensibility and viscoelastic material properties of a healthy, remodeled pregnant cervix.
Topics: Animals; Biglycan; Cervix Uteri; Decorin; Extracellular Matrix; Extracellular Matrix Proteins; Female; Mice; Mice, Knockout; Pregnancy
PubMed: 35348624
DOI: 10.1115/1.4054199 -
PLoS Pathogens Jul 2014Lyme disease spirochetes demonstrate strain- and species-specific differences in tissue tropism. For example, the three major Lyme disease spirochete species, Borrelia...
Lyme disease spirochetes demonstrate strain- and species-specific differences in tissue tropism. For example, the three major Lyme disease spirochete species, Borrelia burgdorferi sensu stricto, B. garinii, and B. afzelii, are each most commonly associated with overlapping but distinct spectra of clinical manifestations. Borrelia burgdorferi sensu stricto, the most common Lyme spirochete in the U.S., is closely associated with arthritis. The attachment of microbial pathogens to cells or to the extracellular matrix of target tissues may promote colonization and disease, and the Lyme disease spirochete encodes several surface proteins, including the decorin- and dermatan sulfate-binding adhesin DbpA, which vary among strains and have been postulated to contribute to strain-specific differences in tissue tropism. DbpA variants differ in their ability to bind to its host ligands and to cultured mammalian cells. To directly test whether variation in dbpA influences tissue tropism, we analyzed murine infection by isogenic B. burgdorferi strains that encode different dbpA alleles. Compared to dbpA alleles of B. afzelii strain VS461 or B. burgdorferi strain N40-D10/E9, dbpA of B. garinii strain PBr conferred the greatest decorin- and dermatan sulfate-binding activity, promoted the greatest colonization at the inoculation site and heart, and caused the most severe carditis. The dbpA of strain N40-D10/E9 conferred the weakest decorin- and GAG-binding activity, but the most robust joint colonization and was the only dbpA allele capable of conferring significant joint disease. Thus, dbpA mediates colonization and disease by the Lyme disease spirochete in an allele-dependent manner and may contribute to the etiology of distinct clinical manifestations associated with different Lyme disease strains. This study provides important support for the long-postulated model that strain-specific variations of Borrelia surface proteins influence tissue tropism.
Topics: Animals; Arthritis, Infectious; Bacterial Proteins; Borrelia burgdorferi; Circular Dichroism; Decorin; Dermatan Sulfate; Female; Flow Cytometry; Humans; Lyme Disease; Mice; Mice, Inbred C3H; Mutation; Myocarditis; Protein Binding; Recombinant Proteins; Species Specificity; Surface Plasmon Resonance; Tropism
PubMed: 25079227
DOI: 10.1371/journal.ppat.1004238 -
The Journal of Biological Chemistry May 2020Extracellular matrix-evoked angiostasis and autophagy within the tumor microenvironment represent two critical, but unconnected, functions of the small leucine-rich...
Extracellular matrix-evoked angiostasis and autophagy within the tumor microenvironment represent two critical, but unconnected, functions of the small leucine-rich proteoglycan, decorin. Acting as a partial agonist of vascular endothelial growth factor 2 (VEGFR2), soluble decorin signals via the energy sensing protein, AMP-activated protein kinase (AMPK), in the autophagic degradation of intracellular vascular endothelial growth factor A (VEGFA). Here, we discovered that soluble decorin evokes intracellular catabolism of endothelial VEGFA that is mechanistically independent of mTOR, but requires an autophagic regulator, paternally expressed gene 3 (PEG3). We found that administration of autophagic inhibitors such as chloroquine or bafilomycin A1, or depletion of autophagy-related 5 (ATG5), results in accumulation of intracellular VEGFA, indicating that VEGFA is a basal autophagic substrate. Mechanistically, decorin increased the VEGFA clearance rate by augmenting autophagic flux, a process that required RAB24 member RAS oncogene family (RAB24), a small GTPase that facilitates the disposal of autophagic compartments. We validated these findings by demonstrating the physiological relevance of this process Mice starved for 48 h exhibited a sharp decrease in overall cardiac and aortic VEGFA that could be blocked by systemic chloroquine treatment. Thus, our findings reveal a unified mechanism for the metabolic control of endothelial VEGFA for autophagic clearance in response to decorin and canonical pro-autophagic stimuli. We posit that the VEGFR2/AMPK/PEG3 axis integrates the anti-angiogenic and pro-autophagic bioactivities of decorin as the molecular basis for tumorigenic suppression. These results support future therapeutic use of decorin as a next-generation protein therapy to combat cancer.
Topics: AMP-Activated Protein Kinases; Autophagy; Decorin; Homeostasis; Human Umbilical Vein Endothelial Cells; Humans; Intracellular Space; Kruppel-Like Transcription Factors; Nutrients; Proteolysis; Vascular Endothelial Growth Factor A; rab GTP-Binding Proteins
PubMed: 32209654
DOI: 10.1074/jbc.RA120.012593 -
EBioMedicine Feb 2020Progressive peritoneal fibrosis is a common complication in patients on long-term peritoneal dialysis (PD). PD-associated peritonitis is a major exacerbating factor. We...
BACKGROUND
Progressive peritoneal fibrosis is a common complication in patients on long-term peritoneal dialysis (PD). PD-associated peritonitis is a major exacerbating factor. We investigated the anti-fibrotic properties of decorin secreted by peritoneal mesothelial cells.
METHODS
Dialysate decorin level in stable PD patients and those with peritonitis was measured. In vitro experiments were conducted to investigate the effect of decorin in fibrotic response in human peritoneal mesothelial cells (HPMC).
FINDINGS
Increasing PD duration was associated with a progressive decrease of dialysate decorin and CA125 levels. Dialysate decorin level correlated with CA125 level. Peritonitis episodes were associated with a massive drop of dialysate decorin, which persisted for over three months despite clinical recovery. Dialysate decorin level correlated with that of TGF-β1, but was inversely related to IL-1β and IL-8. TGF-β1, IL-1β, IL-6, IL-8, or TNF-α reduced decorin secretion in HPMC, but induced fibronectin expression. The effects were mediated in part through increased p38 MAPK and AKT/PI3K phosphorylation. Decorin abrogated the induction of fibronectin expression in mesothelial cells by PD fluids or pro-fibrotic cytokines, through decreased TGF-βRI, p38 MAPK and AKT/PI3K phosphorylation and increased glycogen synthase kinase-3β phosphorylation. Decorin gene-silencing resulted in increased fibronectin expression under these conditions.
INTERPRETATION
Our data demonstrate anti-fibrotic actions of decorin in HPMC, when these cells are subjected to the pro-fibrotic effect of peritoneal dialysate and pro-fibrotic cytokines in PD, especially during peritonitis.
Topics: Aged; Biomarkers; Cytokines; Decorin; Female; Fibronectins; Fibrosis; Gene Knockdown Techniques; Humans; Male; Middle Aged; Peritoneal Dialysis; Peritonitis
PubMed: 32062358
DOI: 10.1016/j.ebiom.2020.102661