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Decorin promotes proliferation and migration of ORS keratinocytes and maintains hair anagen in mice.Experimental Dermatology Nov 2018DECORIN is a prototypical member of the small leucine-rich proteoglycan (SLRP) family that plays important roles in numerous biological processes and cellular biological...
DECORIN is a prototypical member of the small leucine-rich proteoglycan (SLRP) family that plays important roles in numerous biological processes and cellular biological pathways. We previously showed that Decorin expression was highly enhanced in mouse dorsal hair follicles (HFs) during the anagen phase and was reduced during the catagen and telogen phases, suggesting that Decorin might modulate follicular cycling and morphogenesis. In this study, to further clarify the effects of DECORIN on hair cells and the cycling transition, an in vitro overexpression strategy and Decorin-null (Dcn ) mice were used to investigate the effects of DECORIN on outer root sheath (ORS) keratinocytes. DECORIN overexpression significantly enhanced proliferation and migration in ORS keratinocytes in vitro. Moreover, DECORIN overexpression upregulated the mRNA and protein expression levels of WNT10b, β-CATENIN and LEF1. The DECORIN overexpression-induced increase in the proliferation and migration of ORS keratinocytes was partially inhibited by a Wnt/β-catenin inhibitor. Furthermore, Dcn mice had a shortened anagen phase and lower levels of β-catenin expression than were observed in wild-type mice in imaging and histological analyses. Taken together, these findings suggest that DECORIN promotes the proliferation and migration of ORS keratinocytes in vitro and maintains hair anagen in mice.
Topics: Adult; Animals; Cell Movement; Cell Proliferation; Cells, Cultured; Decorin; Down-Regulation; Female; Gene Expression; Hair Follicle; Humans; Keratinocytes; Lymphoid Enhancer-Binding Factor 1; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Middle Aged; Protein Biosynthesis; RNA, Messenger; Transfection; Wnt Proteins; Wnt Signaling Pathway; Wound Healing; Young Adult; beta Catenin
PubMed: 30099770
DOI: 10.1111/exd.13770 -
Oncotarget Jan 2018Decorin (DCN), an extracellular matrix (ECM) protein, belongs to the small leucine-rich proteoglycan family. As a pluripotent molecule, DCN regulates the bioactivities... (Review)
Review
Decorin (DCN), an extracellular matrix (ECM) protein, belongs to the small leucine-rich proteoglycan family. As a pluripotent molecule, DCN regulates the bioactivities of cell growth factors and participates in ECM assembly. Accumulating evidence has shown that DCN acts as a ligand of various cytokines and growth factors by directly or indirectly interacting with the corresponding signalling molecules involved in cell growth, differentiation, proliferation, adhesion and metastasis and that DCN especially plays vital roles in cancer cell proliferation, spread, pro-inflammatory processes and anti-fibrillogenesis. The multifunctional nature of DCN thus enables it to be a potential therapeutic agent for a variety of diseases and shows good prospects for clinical and research applications. DCN, an extracellular matrix (ECM) protein that belongs to the small leucine-rich proteoglycan family, is widely distributed and plays multifunctional roles in the stroma and epithelial cells. Originally, DCN was known as an effective collagen-binding partner for fibrillogenesis [1] and to modulate key biomechanical parameters of tissue integrity in the tendon, skin and cornea [2]; thus, it was named decorin (DCN). Since being initially cloned in 1986, DCN was discovered to be a structural constituent of the ECM [3]. However, the paradigm has been shifted; it has become increasingly evident that in addition to being a matrix structural protein, DCN affects a wide range of biological processes, including cell growth, differentiation, proliferation, adhesion, spread and migration, and regulates inflammation and fibrillogenesis [4-7]. Two main themes for DCN functions have emerged: maintenance of cellular structure and regulation of signal transduction pathways, culminating in anti-tumourigenic effects. Here, we review the interaction network of DCN and emphasize the biological correlations between these interactions, some of which are expected to be therapeutic intervention targets.
PubMed: 29435195
DOI: 10.18632/oncotarget.23869 -
Experimental Eye Research Mar 2022A characteristic rigid spatial arrangement of collagen fibrils in the stroma is critical for corneal transparency. This unique organization of collagen fibrils in...
A characteristic rigid spatial arrangement of collagen fibrils in the stroma is critical for corneal transparency. This unique organization of collagen fibrils in corneal stroma can be impacted by the presence and interactions of proteoglycans and extracellular matrix (ECM) proteins in a corneal microenvironment. Earlier studies revealed that decorin, a leucine-rich proteoglycan in stroma, regulates keratocyte-collagen matrix assembly and wound healing in the cornea. This study investigated the role of decorin in the regulation of stromal fibrillogenesis and corneal transparency in vivo employing a loss-of-function genetic approach using decorin null (dcn) and wild type (dcn) mice and a standard alkali-injury model. A time-dependent ocular examinations with Slit lamp microscope in live animals assessed corneal clarity, haze, and neovascularization levels in normal and injured eyes. Morphometric changes in normal and injured dcn and dcn corneas, post-euthanasia, were analyzed with Masson's Trichrome and Periodic Acid-Schiff (PAS) histology evaluations. The ultrastructure changes in all corneas were investigated with transmission electron microscopy (TEM). Injury to eye produced clinically relevant corneal haze and neovascularization in dcn and dcn mice while corneas of uninjured eyes remained clear and avascular. A clinically significant haze and neovascularization appeared in injured dcn corneas compared to the dcn corneas at day 21 post-injury and not at early tested times. Histological examinations revealed noticeably abnormal morphology and compromised collagen levels in injured dcn corneas compared to the injured/normal dcn and uninjured dcn corneas. TEM analysis exhibited remarkably uneven collagen fibrils size and distribution in the stroma with asymmetrical organization and loose packing in injured dcn corneas than injured/normal dcn and uninjured dcn corneas. The minimum and maximum inter-fibril distances were markedly irregular in injured dcn corneas compared to all other corneas. Together, results of clinical, histological, and ultrastructural investigations in a genetic knockout model suggested that decorin influenced stromal fibrillogenesis and transparency in healing cornea.
Topics: Animals; Burns, Chemical; Corneal Injuries; Decorin; Extracellular Matrix Proteins; Eye Burns; Fibrillar Collagens; Mice; Mice, Inbred C57BL; Mice, Knockout; Mice, Transgenic; Microscopy, Electron, Transmission; Organogenesis; Slit Lamp Microscopy; Sodium Hydroxide; Wound Healing
PubMed: 35031282
DOI: 10.1016/j.exer.2022.108933 -
Molecular Human Reproduction Nov 2021Decorin, a small leucine-rich proteoglycan produced by decidual cells restrains trophoblast differentiation, migration and invasiveness of extra-villous trophoblast...
Decorin, a small leucine-rich proteoglycan produced by decidual cells restrains trophoblast differentiation, migration and invasiveness of extra-villous trophoblast cells. Decidual overproduction of decorin is associated with preeclampsia, and elevated decorin levels in maternal plasma are a predictive biomarker of preeclampsia. Furthermore, decorin plays an autocrine role in maturation of human endometrial stromal cells into decidual cells. Thus, a balanced decorin production by the decidua is critical for healthy pregnancy. However, the molecular mechanisms regulating decorin production by the decidua are unclear. Interleukin-1 beta is an inflammation-associated multi-functional cytokine, and is reported to induce decidualization in primates. Hence, the present study was designed: (i) to test if exogenous Interleukin-1 beta stimulated decorin production by human endometrial stromal cells; and if so, (ii) to identify the cellular source of Interleukin-1 beta in first trimester decidual tissue; (iii) to identify the downstream molecular partners in Interleukin-1 beta mediated decorin production by human endometrial stromal cells. Results revealed that (i) amongst multiple pro-inflammatory cytokines tested, Interleukin-1 beta alone stimulated decorin production by these cells; (ii) both macrophages and decidual cells in first trimester decidua produced Interleukin-1 beta; (iii) Interleukin-1 beta mediated decorin production was dependent on Interleukin-1 receptor activation, followed by activation and nuclear translocation of nuclear factor kappa B and its binding to the decorin promoter. These results reveal that Interleukin-1 beta plays a novel role in inducing decorin production by human endometrial stromal cells by activating nuclear factor kappa B.
Topics: Active Transport, Cell Nucleus; Binding Sites; Cell Line; Decidua; Decorin; Female; Humans; Interleukin-1beta; Macrophages; NF-kappa B; Pregnancy; Pregnancy Trimester, First; Promoter Regions, Genetic; Receptors, Interleukin-1 Type I; Stromal Cells; Up-Regulation
PubMed: 34915564
DOI: 10.1093/molehr/gaab068 -
Matrix Biology : Journal of the... Jan 2019Autophagy, a fundamental and evolutionarily-conserved eukaryotic pathway, coordinates a complex balancing act for achieving both nutrient and energetic requirements for... (Review)
Review
Autophagy, a fundamental and evolutionarily-conserved eukaryotic pathway, coordinates a complex balancing act for achieving both nutrient and energetic requirements for proper cellular function and homeostasis. We have discovered that soluble proteoglycans evoke autophagy in endothelial cells and mitophagy in breast carcinoma cells by directly interacting with receptor tyrosine kinases, including VEGF receptor 2 and Met. Under these circumstances, autophagic regulation is considered "non-canonical" and is epitomized by the bioactivity of the small leucine-rich proteoglycan, decorin. Soluble matrix-derived cues being transduced downstream of receptor engagement converge upon a newly-discovered nexus of autophagic machinery consisting of Peg3 for endothelial cell autophagy and mitostatin for tumor cell mitophagy. In this thematic mini-review, we will provide an overview of decorin-mediated autophagy and mitophagy and propose that regulating intracellular catabolism is the underlying molecular basis for the versatility of decorin as a potent oncosuppressive agent.
Topics: Autophagy; Carrier Proteins; Decorin; Humans; Kruppel-Like Transcription Factors; Metabolism; Mitophagy; Proto-Oncogene Proteins c-met; Signal Transduction; Tumor Suppressor Proteins; Vascular Endothelial Growth Factor Receptor-2
PubMed: 29080840
DOI: 10.1016/j.matbio.2017.10.005 -
The Ocular Surface Jul 2023Small leucine rich proteoglycans (SLRPs) are the largest family of proteoglycans, with 18 members that are subdivided into five classes. SLRPs are small in size and can... (Review)
Review
Small leucine rich proteoglycans (SLRPs) are the largest family of proteoglycans, with 18 members that are subdivided into five classes. SLRPs are small in size and can be present in tissues as glycosylated and non-glycosylated proteins, and the most studied SLRPs include decorin, biglycan, lumican, keratocan and fibromodulin. SLRPs specifically bind to collagen fibrils, regulating collagen fibrillogenesis and the biomechanical properties of tissues, and are expressed at particularly high levels in fibrous tissues, such as the cornea. However, SLRPs are also very active components of the ECM, interacting with numerous growth factors, cytokines and cell surface receptors. Therefore, SLRPs regulate major cellular processes and have a central role in major fundamental biological processes, such as maintaining corneal homeostasis and transparency and regulating corneal wound healing. Over the years, mutations and/or altered expression of SLRPs have been associated with various corneal diseases, such as congenital stromal corneal dystrophy and cornea plana. Recently, there has been great interest in harnessing the various functions of SLRPs for therapeutic purposes. In this comprehensive review, we describe the structural features and the related functions of SLRPs, and how these affect the therapeutic potential of SLRPs, with special emphasis on the use of SLRPs for treating ocular surface pathologies.
Topics: Chondroitin Sulfate Proteoglycans; Extracellular Matrix Proteins; Small Leucine-Rich Proteoglycans; Decorin; Keratan Sulfate; Collagen; Biology
PubMed: 37355022
DOI: 10.1016/j.jtos.2023.06.013 -
Medicine Jul 2022Migration of bladder cancer (BC) cells poses a substantial threat to human health. It is critical to elucidate the mechanism of BC invasion and progression for surgical...
Migration of bladder cancer (BC) cells poses a substantial threat to human health. It is critical to elucidate the mechanism of BC invasion and progression for surgical treatment and the prognosis of patients. Decorin is of interest as an anticancer treatment that can play a vital role in regulating tumorigenesis. The effect of decorin expression on survival in clinical patients was screened and analyzed using bladder urothelial carcinoma data from the Cancer Genome Atlas (TCGA) database. The differential expression of transforming growth factor-β1 (TGF-β1) in tumors was compared against that of normal samples to analyze the correlation between them. MTT, flow cytometry, and Wound/Transwell assays were used to detect cell proliferation, cycle arrest, apoptosis, migration, and invasion. Analysis of TCGA data showed that decorin expression was significantly lower in bladder urothelial carcinoma samples than in normal tissues, while TGF-β1 expression did not change significantly. We found that decorin was correlated with TGF-β1 expression in bladder urothelial cancer. In addition, decorin blocked the G1/S phase by upregulating p21 protein and inhibiting the expression of TGF-β1 and MMP2, promoting the occurrence of apoptosis and inhibiting the proliferation of human BC T24 cells. Moreover, decorin increased the adhesion of tumor cells in vitro, and effectively inhibited cell metastasis. Decorin regulated the expression of TGF-β1 and MMP2 through p21 protein, promoted apoptosis and adhesion, and inhibited the proliferation and metastasis of BC cells.
Topics: Carcinoma, Transitional Cell; Cell Proliferation; Cyclin-Dependent Kinase Inhibitor p21; Decorin; Humans; Matrix Metalloproteinase 2; Transforming Growth Factor beta1; Urinary Bladder Neoplasms
PubMed: 35777025
DOI: 10.1097/MD.0000000000029760 -
Problemy Endokrinologii Jul 2022Myokines are synthesized by myocytes and released into the bloodstream in response to muscle fiber contraction. They have a positive effect on carbohydrate and lipid... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Myokines are synthesized by myocytes and released into the bloodstream in response to muscle fiber contraction. They have a positive effect on carbohydrate and lipid metabolism, muscle mass growth, osteogenesis, increase tissue sensitivity to insulin, counteract inflammation of adipose tissue. The study of their secretion in response to physical activity (FA) can help to personalize the therapy of obesity.
AIM
to study the features of the secretion of myokines in children with constitutionally exogenous obesity during physical activity of different duration and intensity and to evaluate their relationship with the parameters of the body composition.
MATERIALS AND METHODS
26 children (10 boys and 16 girls) were included in the study 15 [13; 16] years old, SDS BMI: +2.91 [2.24; 3.29], with sexual development according to Tanner 4-5. Two groups of 13 people were formed by random distribution. Group I performed FA (walking on a treadmill under the control of heart rate) of different duration: 30 and 60 minutes at the same intensity (less than 3 metabolic equivalents (MET)). Group II - FA of different intensity: low - less than 3 METH and moderate - 3-6 METH with the same duration of 45 minutes. Commercial kits for enzyme immunoassay were used to determine the level of myokines. The assessment of the compositional composition of the body was carried out by bioimpedance analysis (analyzer In Body 770, South Korea) in the morning, on an empty stomach. Statistical processing was carried out using STATISTICA v.12.0 (StatSoftInc., USA). The results are presented in the form of median (Me) and quartiles (Q1; Q3) corresponding to 25 and 75 percentiles. The critical significance level (p) was assumed to be <0.05.
RESULTS
moderate intensity FA leads to a maximum increase in the level of myokines: interleukin-6 (IL-6) by 215.7% and decorin by 34.3%, a decrease in the level of irisin by 16.5%. An hour-long low-intensity workout leads to a moderate increase in the level of IL-6 by 80.5%, to a decrease in the level of irisin by 31.1%. Myostatin increases equally both after 60-minute FA and after moderate intensity FA by 30.9% and 31.8%, respectively. Short low-intensity FA (lasting 30 minutes) it is not accompanied by a significant increase in the expression of myokines. The relationship between the amount of muscle (r=0.65), lean (r=0.62), fat-free mass (r=0.64) and the level of decorin after FA was noted. There was no statistically significant relationship between the parameters of the body composition and the levels of IL-6, myostatin, and irisin. There were no gender differences in both basal and stimulated myokine secretion.
CONCLUSION
Moderate intensity FA and low intensity 60-minute FA are most effective for obese children. A 30-minute low-intensity FN is insufficient to increase the secretion of myokines by skeletal muscles.
Topics: Adolescent; Child; Decorin; Exercise; Female; Fibronectins; Humans; Interleukin-6; Male; Myostatin; Pediatric Obesity
PubMed: 36104971
DOI: 10.14341/probl13138 -
Cancer Microenvironment : Official... Dec 2017Metaplastic breast carcinoma (MBC) is a rare subtype of invasive breast cancer and has poor prognosis. In general, cancers are heterogeneous cellular masses comprised of...
Metaplastic breast carcinoma (MBC) is a rare subtype of invasive breast cancer and has poor prognosis. In general, cancers are heterogeneous cellular masses comprised of different cell types and their extracellular matrix (ECM). However, little is known about the composition of the ECM and its constituents in MBC. Decorin is a ubiquitous ECM macromolecule known of its oncosuppressive activity. As such, it provides an intriguing molecule in the development of novel therapeutics for different malignancies such as MBC. In this study, decorin immunoreactivity and the effect of adenoviral decorin cDNA (Ad-DCN) transduction were examined in MBC. Multiple immunohistochemical stainings were used to characterize a massive breast tumour derived from an old woman. Furthermore, three-dimensional (3D) explant cultures derived from the tumour were transduced with Ad-DCN to study the effect of the transduction on the explants. The MBC tumour was shown to be completely negative for decorin immunoreactivity demonstrating that the malignant cells were not able to synthesize decorin. Ad-DCN transduction resulted in a markedly altered cytological phenotype of MBC explants by decreasing the amount of atypical cells and by inhibiting cell proliferation. The results of this study support approaches to develop new, decorin-based adjuvant therapies for MBC.
PubMed: 28653173
DOI: 10.1007/s12307-017-0195-8 -
Proceedings of the National Academy of... Apr 2024The complex interplay between malignant cells and the cellular and molecular components of the tumor stroma is a key aspect of cancer growth and development. These...
The complex interplay between malignant cells and the cellular and molecular components of the tumor stroma is a key aspect of cancer growth and development. These tumor-host interactions are often affected by soluble bioactive molecules such as proteoglycans. Decorin, an archetypical small leucine-rich proteoglycan primarily expressed by stromal cells, affects cancer growth in its soluble form by interacting with several receptor tyrosine kinases (RTK). Overall, decorin leads to a context-dependent and protracted cessation of oncogenic RTK activity by attenuating their ability to drive a prosurvival program and to sustain a proangiogenic network. Through an unbiased transcriptomic analysis using deep RNAseq, we identified that decorin down-regulated a cluster of tumor-associated genes involved in lymphatic vessel (LV) development when systemically delivered to mice harboring breast carcinoma allografts. We found that Lyve1 and Podoplanin, two established markers of LVs, were markedly suppressed at both the mRNA and protein levels, and this suppression correlated with a significant reduction in tumor LVs. We further identified that soluble decorin, but not its homologous proteoglycan biglycan, inhibited LV sprouting in an ex vivo 3D model of lymphangiogenesis. Mechanistically, we found that decorin interacted with vascular endothelial growth factor receptor 3 (VEGFR3), the main lymphatic RTK, and its activity was required for the decorin-mediated block of lymphangiogenesis. Finally, we identified that Lyve1 was in part degraded via decorin-evoked autophagy in a nutrient- and energy-independent manner. These findings implicate decorin as a biological factor with antilymphangiogenic activity and provide a potential therapeutic agent for curtailing breast cancer growth and metastasis.
Topics: Decorin; Lymphangiogenesis; Animals; Mice; Humans; Female; Breast Neoplasms; Lymphatic Vessels; Cell Line, Tumor; Disease Progression; Vesicular Transport Proteins; Membrane Glycoproteins; Gene Expression Regulation, Neoplastic
PubMed: 38652741
DOI: 10.1073/pnas.2317760121