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Molecules (Basel, Switzerland) Nov 2022Changes in the expression of various genes, including pregnancy-associated hormone receptors and extracellular matrix proteins, have been suggested to play a significant...
Changes in the expression of various genes, including pregnancy-associated hormone receptors and extracellular matrix proteins, have been suggested to play a significant role in bovine placental development. This study aimed to examine the influence of sex steroids and PGF2α on decorin (DCN) expression in the epithelial cells of bovine caruncle in early−mid pregnancy in cows. The expression patterns of DCN, PTGFR, PGR and ESR1 were analyzed by RT-qPCR and Western blotting in primary caruncular epithelial cell cultures (PCECC) and placental tissue homogenates derived from the 2nd and 4th months of pregnancy. PCECC were found to express DCN, PTGFR, PGR and ESR1. The intensity of PGR staining was higher in cells derived from the 4th month of pregnancy (p < 0.05). The 17β-estradiol, progesterone and PGF2α have not been shown to affect DCN expression. PGF2α decreased PTGFR expression in cells derived from the 4th month of gestation (p < 0.05). In conclusion, the results of the present preliminary study showed that the expression of the PTGFR, ESR1, PGR and DCN in PCECC does not vary throughout early−mid pregnancy. Further studies should be carried out to observe the relationship between hormonal status and cellular adhesion to determine their importance for properly developing placentation and pregnancy in cows.
Topics: Cattle; Pregnancy; Female; Animals; Dinoprost; Decorin; Placenta; Progesterone; Epithelial Cells
PubMed: 36364246
DOI: 10.3390/molecules27217420 -
Frontiers in Medicine 2023Exposure to solar radiation can cause a range of skin damage, including sunburn, erythema, skin carcinogenesis, the release of reactive oxygen species (ROS),...
INTRODUCTION
Exposure to solar radiation can cause a range of skin damage, including sunburn, erythema, skin carcinogenesis, the release of reactive oxygen species (ROS), inflammation, DNA damage, and photoaging. Other wavelengths beyond UVB, such as UVA, blue light, and infrared radiation, can also contribute to the harmful effects of solar radiation. Reconstructed full-thickness human skin has the potential to serve as effective predictive in vitro tools for evaluating the effects of solar radiation on the skin. The aim of this work was to evaluate the damaging effects of UVA, blue light, and infrared radiation in a full-thickness skin model in terms of viability, inflammation, photoaging, tissue damage, photocarcinogenesis.
METHODS
Full thickness skin models were purchased from Henkel (Phenion FT; Düsseldorf, Germany), and irradiated with increasing doses of UVA, blue light, or infrared radiation. Different endpoints were analyzed on the tissues: Hematoxylin-eosin staining, inflammation mediators, photoaging-related dermal markers and oxidative stress marker GPX1, evaluated by real-time quantitative PCR, as well as photocarcinogenesis markers by Western Blot.
RESULTS AND DISCUSSION
The results showed differential responses in cytokine release for each light source. In terms of photoaging biomarkers, collagen, metalloproteinases 1 and 9, elastin, and decorin were modulated by UVA and blue light exposure, while not all these markers were affected by infrared radiation. Furthermore, exposure to UVA and blue light induced loss of fibroblasts and modulation of the photocarcinogenesis markers p53 and p21. In conclusion, the presented results suggest that the various wavelengths of solar light have distinct and differential damaging effects on the skin. Understanding the differential effects of UVA, blue light, and infrared radiation can serve as a valuable tool to investigate the efficacy of photoprotective agents in full thickness skin models.
PubMed: 38105899
DOI: 10.3389/fmed.2023.1267409 -
Matrix Biology : Journal of the... Jan 2021The tumor microenvironment encompasses a complex cellular network that includes cancer-associated fibroblasts, inflammatory cells, neo-vessels, and an extracellular...
The tumor microenvironment encompasses a complex cellular network that includes cancer-associated fibroblasts, inflammatory cells, neo-vessels, and an extracellular matrix enriched in angiogenic growth factors. Decorin is one of the main components of the tumor stroma, but it is not expressed by cancer cells. Lack of this proteoglycan correlates with down-regulation of E-cadherin and induction of β-catenin signaling. In this study, we investigated the role of a decorin-deficient tumor microenvironment in colon carcinoma progression and metastasis. We utilized an established model of colitis-associated cancer by administering Azoxymethane/Dextran sodium sulfate to adult wild-type and Dcn mice. We discovered that after 12 weeks, all the animals developed intestinal tumors independently of their genotype. However, the number of intestinal neoplasms was significantly higher in the Dcn microenvironment vis-à-vis wild-type mice. Mechanistically, we found that under unchallenged basal conditions, the intestinal epithelium of the Dcn mice showed a significant increase in the protein levels of epithelial-mesenchymal transition associated factors including Snail, Slug, Twist, and MMP2. In comparison, in the colitis-associated cancer evoked in the Dcn mice, we found that intercellular adhesion molecule 1 (ICAM-1) was also significantly increased, in parallel with epithelial-mesenchymal transition signaling pathway-related factors. Furthermore, a combined Celecoxib/decorin treatment revealed a promising therapeutic efficacy in treating human colorectal cancer cells, in decorin-deficient animals. Collectively, our results shed light on colorectal cancer progression and provide a protein-based therapy, i.e., treatment using recombinant decorin, to target the tumor microenvironment.
Topics: Animals; Azoxymethane; Cadherins; Cancer-Associated Fibroblasts; Celecoxib; Colitis-Associated Neoplasms; Colonic Neoplasms; Decorin; Epithelial-Mesenchymal Transition; Extracellular Matrix; Humans; Mice; Neoplasm Metastasis; Proteoglycans; Tumor Microenvironment; beta Catenin
PubMed: 33065248
DOI: 10.1016/j.matbio.2020.10.001 -
American Journal of Physiology. Lung... May 2021Mesenchymal stromal cells (MSCs) may provide crucial support in the regeneration of destructed alveolar tissue (emphysema) in chronic obstructive pulmonary disease...
Mesenchymal stromal cells (MSCs) may provide crucial support in the regeneration of destructed alveolar tissue (emphysema) in chronic obstructive pulmonary disease (COPD). We hypothesized that lung-derived MSCs (LMSCs) from patients with emphysema are hampered in their repair capacity, either intrinsically or due to their interaction with the damaged microenvironment. LMSCs were isolated from the lung tissue of controls and patients with severe emphysema and characterized at baseline. In addition, LMSCs were seeded onto control and emphysematous decellularized lung tissue scaffolds and assessed for deposition of extracellular matrix (ECM). We observed no differences in surface markers, differentiation/proliferation potential, and expression of ECM genes between control- and COPD-derived LMSCs. Notably, COPD-derived LMSCs displayed lower expression of and messenger RNA (mRNA) and hepatocyte growth factor (HGF) and decorin protein. When seeded on control decellularized lung tissue scaffolds, control- and COPD-derived LMSCs showed no differences in engraftment, proliferation, or survival within 2 wk, with similar ability to deposit new matrix on the scaffolds. Moreover, LMSC numbers and the ability to deposit new matrix were not compromised on emphysematous scaffolds. Collectively, our data show that LMSCs from patients with COPD compared with controls show less expression of mRNA, HGF mRNA and protein, and decorin protein, whereas other features including the mRNA expression of various ECM molecules are unaffected. Furthermore, COPD-derived LMSCs are capable of engraftment, proliferation, and functioning on native lung tissue scaffolds. The damaged, emphysematous microenvironment as such does not hamper the potential of LMSCs. Thus, specific intrinsic deficiencies in growth factor production by diseased LMSCs may contribute to impaired alveolar repair in emphysema.
Topics: Adult; Aged; Aged, 80 and over; Case-Control Studies; Cell Differentiation; Cell Proliferation; Cells, Cultured; Extracellular Matrix; Female; Gene Expression Regulation; Humans; Lung; Male; Mesenchymal Stem Cells; Middle Aged; Pulmonary Disease, Chronic Obstructive; Pulmonary Emphysema; Tissue Scaffolds
PubMed: 33656381
DOI: 10.1152/ajplung.00147.2020 -
Journal of Biomechanical Engineering May 2022Tendon is a connective tissue that transmits loads from muscle to bone, while ligament is a similar tissue that stabilizes joint articulation by connecting bone to bone.... (Review)
Review
Tendon is a connective tissue that transmits loads from muscle to bone, while ligament is a similar tissue that stabilizes joint articulation by connecting bone to bone. The 70-90% of tendon and ligament's extracellular matrix (ECM) is composed of a hierarchical collagen structure that provides resistance to deformation primarily in the fiber direction, and the remaining fraction consists of a variety of non-collagenous proteins, proteoglycans, and glycosaminoglycans (GAGs) whose mechanical roles are not well characterized. ECM constituents such as elastin, the proteoglycans decorin, biglycan, lumican, fibromodulin, lubricin, and aggrecan and their associated GAGs, and cartilage oligomeric matrix protein (COMP) have been suggested to contribute to tendon and ligament's characteristic quasi-static and viscoelastic mechanical behavior in tension, shear, and compression. The purpose of this review is to summarize existing literature regarding the contribution of the non-collagenous ECM to tendon and ligament mechanics, and to highlight key gaps in knowledge that future studies may address. Using insights from theoretical mechanics and biology, we discuss the role of the non-collagenous ECM in quasi-static and viscoelastic tensile, compressive, and shear behavior in the fiber direction and orthogonal to the fiber direction. We also address the efficacy of tools that are commonly used to assess these relationships, including enzymatic degradation, mouse knockout models, and computational models. Further work in this field will foster a better understanding of tendon and ligament damage and healing as well as inform strategies for tissue repair and regeneration.
Topics: Animals; Collagen; Decorin; Extracellular Matrix; Extracellular Matrix Proteins; Glycosaminoglycans; Ligaments; Mice; Tendons
PubMed: 34802057
DOI: 10.1115/1.4053086 -
The Journal of Maternal-fetal &... Dec 2023This study analyzed the levels of peripheral blood tumor necrosis factor-α (TNF-α), Decorin (DCN) and Mitogen-activated protein kinase 1 (MAPK1) mRNA in neutrophils...
This study analyzed the levels of peripheral blood tumor necrosis factor-α (TNF-α), Decorin (DCN) and Mitogen-activated protein kinase 1 (MAPK1) mRNA in neutrophils of patients with preeclampsia and their correlations, in order to provide more thoughts on the diagnosis and treatment of clinical patients. 81 patients with preeclampsia who had regular prenatal checkups and delivered in our hospital from June 2020 to April 2022 were analyzed, including 26 patients with early-onset and 55 patients with late-onset, and 50 pregnant women with normal pregnancy who had prenatal checkups and delivered in our hospital during the same period were selected as the control group. Record the clinical data of patients, record the expression of peripheral blood TNF-α, DCN and neutrophils MAPK1 mRNA of patients with early-onset, late-onset and the control group, and record the correlation between DCN level, MAPK1 mRNA expression and TNF-α level of patients with preeclampsia. The diastolic and systolic blood pressures were significantly higher in early-onset and late-onset patients, and the gestational week of delivery was significantly lower in early-onset and late-onset patients, respectively ( < .05); there was no statistically significant difference in the average age, BMI, average pregnancy time, and average births between the three groups ( > .05). The expressions of peripheral blood TNF-α, DCN, and neutrophils MAPK1 mRNA of the early-onset and late-onset groups were all higher than those in the control group ( < .05); and the expressions of TNF-α, DCN, and MAPK1 mRNA in the peripheral blood of the early-onset group were all higher than those in the late-onset group ( < .05); correlation analysis showed that DCN level and TNF-α level in patients with preeclampsia were positively correlated ( = 0.98639, < .05); Neutrophils MAPK1 mRNA expression and TNF-α level were positively correlated ( = 0.9611, < .05). TNF-α, DCN and neutrophils MAPK1 mRNA were all highly expressed in the peripheral blood of patients with pre-eclampsia and were more significantly elevated in patients with early-onset preeclampsia, and the expression levels of DCN and MAPK1 mRNA were positively correlated with TNF-α levels. It is possible that all three factors are involved in the pathogenesis of preeclampsia, and are expected to be used as indicators for early prediction and diagnosis.
Topics: Female; Humans; Pregnancy; Clinical Relevance; Decorin; Mitogen-Activated Protein Kinase 1; Neutrophils; Pre-Eclampsia; Tumor Necrosis Factor-alpha; RNA, Messenger
PubMed: 36852440
DOI: 10.1080/14767058.2023.2183745 -
Frontiers in Oncology 2020Hepatocellular carcinoma (HCC) represents one of the most frequent type of primary liver cancers. Decorin, a small leucine-rich proteoglycan of the extracellular matrix,...
Hepatocellular carcinoma (HCC) represents one of the most frequent type of primary liver cancers. Decorin, a small leucine-rich proteoglycan of the extracellular matrix, represents a powerful tumor cell growth and migration inhibitor by hindering receptor tyrosine kinases and inducing p21. In this study, first we tested decorin expression in HCCs utilizing data, as well as formalin fixed paraffin embedded tissue samples of HCC in a tissue microarray (TMA). data revealed that DCN/SMA mRNA ratio is decreased in HCC compared to normal tissues and follows the staging of the disease. Among TMA samples, 52% of HCCs were decorin negative, 33% exhibited low, and 15% high decorin levels corroborating results. In addition, applying conditioned media of hepatoma cells inhibited decorin expression in LX2 stellate cells . These results raise the possibility that decorin acts as a tumor suppressor in liver cancer and that is why its expression decreased in HCCs. To further test the protective role of decorin, the proteoglycan was overexpressed in a mouse model of hepatocarcinogenesis evoked by thioacetamide (TA). After transfection, the excessive proteoglycan amount was mainly detected in hepatocytes around the central veins. Upon TA-induced hepatocarcinogenesis, the highest tumor count was observed in mice with no decorin production. Decorin gene delivery reduced tumor formation, in parallel with decreased pEGFR, increased pIGF1R levels, and with concomitant induction of pAkt (T308) and phopho-p53, suggesting a novel mechanism of action. Our results suggest the idea that decorin can be utilized as an anti-cancer agent.
PubMed: 32477937
DOI: 10.3389/fonc.2020.00645 -
Osteoarthritis and Cartilage Aug 2021
Topics: Cartilage, Articular; Decorin; Extracellular Matrix; Humans; Osteoarthritis; Proteoglycans
PubMed: 33932566
DOI: 10.1016/j.joca.2021.04.010 -
FASEB Journal : Official Publication of... Jun 2020Obesity is a risk factor for breast cancer in postmenopausal and high-risk premenopausal women. Changes within the obese breast microenvironment may increase breast...
Obesity is a risk factor for breast cancer in postmenopausal and high-risk premenopausal women. Changes within the obese breast microenvironment may increase breast cancer risk. Transforming growth factor beta-1 (TGFβ1) is a major regulator of mammary epithelial stem/progenitor cells, and its activity is dysregulated under conditions of obesity. Using a high-fat diet model of obesity in mice and breast tissue from women, we observed that TGFβ1 activity is reduced in breast epithelial cells in obesity. Breast ducts and lobules demonstrated increased decorin in the extracellular matrix (ECM) surrounding epithelial cells, and we observed that decorin and latent TGFβ1 complexed together. Under conditions of obesity, macrophages expressed higher levels of decorin and were significantly increased in number surrounding breast epithelial cells. To investigate the relationship between macrophages and decorin expression, we treated obese mice with either IgG control or anti-F4/80 antibodies to deplete macrophages. Mice treated with anti-F4/80 antibodies demonstrated reduced decorin surrounding mammary ducts and enhanced TGFβ1 activity within mammary epithelial cells. Given the role of TGFβ1 as a tumor suppressor, reduced epithelial TGFβ1 activity and enhanced TGFβ1 within the ECM of obese mammary tissue may enhance breast cancer risk.
Topics: Adolescent; Adult; Animals; Breast; Breast Neoplasms; Cells, Cultured; Diet, High-Fat; Epithelial Cells; Extracellular Matrix; Female; Humans; Macrophages; Mammary Glands, Animal; Mammary Glands, Human; Mice; Mice, Inbred C57BL; Mice, Obese; Middle Aged; Obesity; Stem Cells; Transforming Growth Factor beta1; Tumor Microenvironment; Young Adult
PubMed: 32359100
DOI: 10.1096/fj.202000228RR -
Journal of Ovarian Research Feb 2020DCN (decorin) is a proteoglycan known to be involved in regulating cell proliferation, collagen fibril organization and migration. In our global transcriptome...
BACKGROUND
DCN (decorin) is a proteoglycan known to be involved in regulating cell proliferation, collagen fibril organization and migration. In our global transcriptome RNA-sequencing approach to systematically identify new ovulation-associated genes, DCN was identified as one of the highly regulated genes. We therefore hypothesize that DCN may have a role in ovulatory processes such as cell migration and proliferation.
AIM
To characterize the expression, regulation and function of the proteoglycan DCN in the human ovarian follicles during the preovulatory period.
METHODS
The in-vivo expression of DCN mRNA in mural (MGCs) and cumulus (CGCs) granulosa cells was characterized using quantitative RT-PCR and western blot. A signaling study was performed by treating human MGCs cultures with gonadotropins and different stimulators and inhibitors to determine their effect on DCN expression by qRT- PCR and elucidate the pathways regulating these proteins. In a functional study, KGN granulosa cell line was used to study cell migration with a scratch assay.
RESULTS
DCN mRNA expression was significantly higher in MGCs compared to CGCs. DCN mRNA was significantly higher in CGCs surrounding mature metaphase II (MII) oocytes compared to CGCs of germinal vesicle (GV) and metaphase I (MI) oocytes. hCG significantly increased DCN mRNA and protein expression levels in cultured MGCs. Using signal transduction activators and inhibitors, we demonstrated that DCN induction by LH/hCG is carried out via PKA, PKC, ERK/MEK, and PI3K pathways. We showed that DCN expression is also induced in high-density cell cultures, in a dose-dependent pattern. In addition, progesterone induced a significant increase in DCN secretion to the media. MGCs from follicles of endometriosis patients exhibited reduced (about 20% of) mRNA transcriptions levels compared to MGCs follicles of control patients. More significantly, we found that DCN has an inhibiting effect on KGN cell migration.
CONCLUSIONS
Our study indicates that DCN is a unique ovulatory gene. Our findings support the hypothesis that DCN plays an important new role during the preovulatory period and ovulation, and stress its involvement in endometriosis infertility. A better understanding of DCN role in ovulation and endometriosis may provide treatment for some types of infertility.
Topics: Cells, Cultured; Decorin; Female; Humans; Ovarian Follicle; Ovulation; Prospective Studies; RNA, Messenger
PubMed: 32041647
DOI: 10.1186/s13048-020-0612-3