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Theranostics 2022Recurrent pregnancy loss (RPL) is a distressing disorder that seriously affects the physical and psychological health of women. RPL is also a sentinel risk marker for...
Recurrent pregnancy loss (RPL) is a distressing disorder that seriously affects the physical and psychological health of women. RPL is also a sentinel risk marker for future obstetric complications and warrants in-depth investigation. Abnormal polarization and functions of decidual macrophages are associated with RPL; however, the underlying mechanisms remain poorly understood. Decorin expression, localization, and content in the decidua of women with normal pregnancy (NP) and those with RPL were measured using reverse transcription-quantitative polymerase chain reaction (RT-qPCR), western blotting, immunofluorescence, and enzyme-linked immunosorbent assay. The profiles of decidual macrophage subsets were determined using flow cytometry and immunofluorescence in both groups. The correlation between decorin content and the proportion of decidual macrophage subsets in the decidua of early NP women was determined using Pearson analysis. The effects of decorin on the polarization and functions of macrophages were assessed in an model of Raw264.7 cells via flow cytometry, western blotting, and RT-qPCR. Moreover, the mitochondrial metabolism in Raw264.7 cells under decorin administration was measured via flow cytometry, western blotting, and immunofluorescence. Thirty-three pregnant mice were included in the model and underwent different treatments. The embryo abortion rate, macrophage phenotype in the spleen and uteri, and placental development were evaluated using flow cytometry and hematoxylin-eosin staining. Decorin, derived from decidual stromal cells, was highly expressed in the decidua of women with RPL. A positive correlation between decorin content and the proportion of M1-like macrophages was also observed in the decidua of early NP women. studies showed that decorin treatment inhibited macrophage polarization to M2-like subsets and boosted the inflammatory response, which was related to enhanced anaerobic glycolysis, increased mitochondrial membrane potential and intracellular reactive oxygen species levels, reduced mitochondrial mass, and activation of the myeloid differentiation primary response 88-nuclear factor-κB signaling pathway. Adoptive transfer of decorin-treated bone marrow-derived macrophages in pregnant C57BL/6 mice increased the embryo absorption, accompanied by impaired fetal vascularization. Decidual stromal cell-derived decorin can polarize decidual macrophages toward the M1 phenotype by regulating mitochondrial metabolism, resulting in the occurrence of RPL.
Topics: Animals; Female; Humans; Mice; Pregnancy; Abortion, Habitual; Decidua; Decorin; Macrophages; Mice, Inbred C57BL; Mitochondria; Placenta
PubMed: 36438479
DOI: 10.7150/thno.78467 -
Cells Dec 2022Decorin is an archetypal member of the small leucine-rich proteoglycan gene family and is involved in various biological functions and many signaling networks,... (Review)
Review
Decorin is an archetypal member of the small leucine-rich proteoglycan gene family and is involved in various biological functions and many signaling networks, interacting with extra-cellular matrix (ECM) components, growth factors, and receptor tyrosine kinases. Decorin also modulates the growth factors, cell proliferation, migration, and angiogenesis. It has been reported to be involved in many ischemic and fibrotic eye diseases, such as congenital stromal dystrophy of the cornea, anterior subcapsular fibrosis of the lens, proliferative vitreoretinopathy, et al. Furthermore, recent evidence supports its role in secondary posterior capsule opacification (PCO) after cataract surgery. The expression of decorin mRNA in lens epithelial cells in vitro was found to decrease upon transforming growth factor (TGF)-β-2 addition and increase upon fibroblast growth factor (FGF)-2 addition. Wound healing of the injured lens in mice transgenic for lens-specific human decorin was promoted by inhibiting myofibroblastic changes. Decorin may be associated with epithelial-mesenchymal transition and PCO development in the lens. Gene therapy and decorin administration have the potential to serve as excellent therapeutic approaches for modifying impaired wound healing, PCO, and other eye diseases related to fibrosis and angiogenesis. In this review, we present findings regarding the roles of decorin in the lens and ocular diseases.
Topics: Mice; Animals; Humans; Decorin; Lens, Crystalline; Capsule Opacification; Epithelial Cells; Fibrosis
PubMed: 36611867
DOI: 10.3390/cells12010074 -
International Journal of Molecular... May 2021Colorectal cancer (CRC) is one of the main causes of cancer death in the world. Post-translational modifications (PTMs) have been extensively studied in malignancies due... (Review)
Review
Colorectal cancer (CRC) is one of the main causes of cancer death in the world. Post-translational modifications (PTMs) have been extensively studied in malignancies due to its relevance in tumor pathogenesis and therapy. This review is focused on the dysregulation of glycosyltransferase expression in CRC and its impact in cell function and in several biological pathways associated with CRC pathogenesis, prognosis and therapeutic approaches. Glycan structures act as interface molecules between cells and their environment and in several cases facilitate molecule function. CRC tissue shows alterations in glycan structures decorating molecules, such as annexin-1, mucins, heat shock protein 90 (Hsp90), β1 integrin, carcinoembryonic antigen (CEA), epidermal growth factor receptor (EGFR), insulin-like growth factor-binding protein 3 (IGFBP3), transforming growth factor beta (TGF-β) receptors, Fas (CD95), PD-L1, decorin, sorbin and SH3 domain-containing protein 1 (SORBS1), CD147 and glycosphingolipids. All of these are described as key molecules in oncogenesis and metastasis. Therefore, glycosylation in CRC can affect cell migration, cell-cell adhesion, actin polymerization, mitosis, cell membrane repair, apoptosis, cell differentiation, stemness regulation, intestinal mucosal barrier integrity, immune system regulation, T cell polarization and gut microbiota composition; all such functions are associated with the prognosis and evolution of the disease. According to these findings, multiple strategies have been evaluated to alter oligosaccharide processing and to modify glycoconjugate structures in order to control CRC progression and prevent metastasis. Additionally, immunotherapy approaches have contemplated the use of neo-antigens, generated by altered glycosylation, as targets for tumor-specific T cells or engineered CAR (Chimeric antigen receptors) T cells.
Topics: Annexin A1; Colorectal Neoplasms; Decorin; ErbB Receptors; Gene Expression Regulation, Neoplastic; Glycosphingolipids; Glycosylation; Glycosyltransferases; Humans; Immunotherapy, Adoptive; Insulin-Like Growth Factor Binding Protein 3; Integrin beta1; Microfilament Proteins; Mucins; Neoplasm Proteins; Protein Processing, Post-Translational; fas Receptor
PubMed: 34070747
DOI: 10.3390/ijms22115822 -
Journal of Immunology Research 2022Decorin is an extracellular matrix protein that belongs to the family of small leucine-rich proteoglycans. As a matrix protein, the first discovered role of decorin is... (Review)
Review
Decorin is an extracellular matrix protein that belongs to the family of small leucine-rich proteoglycans. As a matrix protein, the first discovered role of decorin is participating in collagen fibril formation. Many other functions of decorin in various biological processes have been subsequently identified. Decorin is involved in an extensive signaling network and can interact with other extracellular matrix components, growth factors, receptor tyrosine kinases, and various proteases. Decorin has been shown to be involved in wound repair, cell cycle, angiogenesis, tumor metastasis, and autophagy. Recent evidence indicates that it also plays a role in immune regulation and inflammatory diseases. This review summarizes the characteristics of decorin in immune and inflammatory diseases, including inflammatory bowel disease (IBD), Sjögren's syndrome (SS), chronic obstructive pulmonary disease (COPD), IgA nephropathy, rheumatoid arthritis (RA), spondyloarthritis (SpA), osteoarthritis, multiple sclerosis (MS), idiopathic inflammatory myopathies (IIM), and systemic sclerosis (SSc) and discusses the potential role in these disorders.
Topics: Autoimmune Diseases; Decorin; Extracellular Matrix; Extracellular Matrix Proteins; Humans; Inflammation; Neovascularization, Pathologic; Proteoglycans
PubMed: 36033387
DOI: 10.1155/2022/1283383 -
Advanced Science (Weinheim,... Mar 2022Traumatic brain injury (TBI) is a risk factor for posttraumatic stress disorder (PTSD). Augmented fear is a defining characteristic of PTSD, and the amygdala is...
Single-Nucleus RNA Sequencing Reveals that Decorin Expression in the Amygdala Regulates Perineuronal Nets Expression and Fear Conditioning Response after Traumatic Brain Injury.
Traumatic brain injury (TBI) is a risk factor for posttraumatic stress disorder (PTSD). Augmented fear is a defining characteristic of PTSD, and the amygdala is considered the main brain region to process fear. The mechanism by which the amygdala is involved in fear conditioning after TBI is still unclear. Using single-nucleus RNA sequencing (snRNA-seq), transcriptional changes in cells in the amygdala after TBI are investigated. In total, 72 328 nuclei are obtained from the sham and TBI groups. 7 cell types, and analysis of differentially expressed genes (DEGs) reveals widespread transcriptional changes in each cell type after TBI are identified. In in vivo experiments, it is demonstrated that Decorin (Dcn) expression in the excitatory neurons of the amygdala significantly increased after TBI, and Dcn knockout in the amygdala mitigates TBI-associated fear conditioning. Of note, this effect is caused by a Dcn-mediated decrease in the expression of perineuronal nets (PNNs), which affect the glutamate-γ-aminobutyric acid balance in the amygdala. Finally, the results suggest that Dcn functions by interacting with collagen VI α3 (Col6a3). Consequently, the findings reveal transcriptional changes in different cell types of the amygdala after TBI and provide direct evidence that Dcn relieves fear conditioning by regulating PNNs.
Topics: Amygdala; Animals; Brain Injuries, Traumatic; Decorin; Fear; Mice; Sequence Analysis, RNA
PubMed: 35038242
DOI: 10.1002/advs.202104112 -
International Journal of Molecular... Jan 2021Proteoglycan (PG) is a glycosaminoglycan (GAG)-conjugated protein essential for maintaining tissue strength and elasticity. The most abundant skin PGs, biglycan and...
Proteoglycan (PG) is a glycosaminoglycan (GAG)-conjugated protein essential for maintaining tissue strength and elasticity. The most abundant skin PGs, biglycan and decorin, have been reported to decrease as skin ages. Insulin-like growth factor-1 (IGF-1) is important in various physiological functions such as cell survival, growth, and apoptosis. It is well known that the serum level of IGF-1 decreases with age. Therefore, we investigated whether and how IGF-1 affects biglycan and decorin. When primary cultured normal human dermal fibroblasts (NHDFs) were treated with IGF-1, protein levels of biglycan and decorin increased, despite no difference in mRNA expression. This increase was not inhibited by transcription blockade using actinomycin D, suggesting that it is mediated by IGF-1-induced enhanced translation. Additionally, both mRNA and protein expression of ADAMTS5, a PG-degrading enzyme, were decreased in IGF-1-treated NHDFs. Knockdown of ADAMTS5 via RNA interference increased protein expression of biglycan and decorin. Moreover, mRNA and protein expression of ADAMTS5 increased in aged human skin tissues compared to young tissue. Overall, IGF-1 increases biglycan and decorin, which is achieved by improving protein translation to increase synthesis and preventing ADAMTS5-mediated degradation. This suggests a new role of IGF-1 as a regulator for biglycan and decorin in skin aging process.
Topics: ADAMTS5 Protein; Adolescent; Adult; Aged; Aged, 80 and over; Biglycan; Cells, Cultured; Child; Decorin; Down-Regulation; Female; Fibroblasts; Gene Expression Profiling; Gene Knockdown Techniques; Healthy Volunteers; Humans; Insulin-Like Growth Factor I; Male; Primary Cell Culture; Protein Biosynthesis; Proteolysis; Skin; Skin Aging; Up-Regulation; Young Adult
PubMed: 33573338
DOI: 10.3390/ijms22031403 -
American Journal of Physiology. Cell... Mar 2022Decorin is a stromal-derived prototype member of the small leucine-rich proteoglycan gene family. In addition to its functions as a regulator of collagen fibrillogenesis... (Review)
Review
Decorin is a stromal-derived prototype member of the small leucine-rich proteoglycan gene family. In addition to its functions as a regulator of collagen fibrillogenesis and TGF-β activity soluble decorin acts as a pan-receptor tyrosine kinase (RTK) inhibitor. Decorin binds to various RTKs including EGFR HER2 HGFR/Met VEGFR2 TLR and IGFR. Although the molecular mechanism for the action of decorin on these receptors is not entirely elucidated overall decorin evokes transient activation of these receptors with suppression of downstream signaling cascades culminating in growth inhibition followed by their physical downregulation via caveosomal internalization and degradation. In the case of Met decorin leads to decreased β-catenin signaling pathway and growth suppression. As most of these RTKs are responsible for providing a growth advantage to cancer cells the result of decorin treatment is oncosuppression. Another decorin-driven mechanism to restrict cancer growth and dissemination is by impeding angiogenesis via vascular endothelial growth factor receptor 2 (VEGFR2) and the concurrent activation of protracted endothelial cell autophagy. In this review we will dissect the multiple roles of decorin in cancer biology and its potential use as a next-generation protein-based adjuvant therapy to combat cancer.
Topics: Autophagy; Carrier Proteins; Decorin; Extracellular Matrix Proteins; Humans; Neoplasms; Receptor Protein-Tyrosine Kinases; Signal Transduction; Vascular Endothelial Growth Factor A
PubMed: 35171698
DOI: 10.1152/ajpcell.00016.2022 -
Matrix Biology : Journal of the... Sep 2016Decorin, a prototype small leucine-rich proteoglycan, regulates a vast array of cellular processes including collagen fibrillogenesis, wound repair, angiostasis, tumor... (Review)
Review
Decorin, a prototype small leucine-rich proteoglycan, regulates a vast array of cellular processes including collagen fibrillogenesis, wound repair, angiostasis, tumor growth, and autophagy. This functional versatility arises from a wide array of decorin/protein interactions also including interactions with its single glycosaminoglycan side chain. The decorin-binding partners encompass numerous categories ranging from extracellular matrix molecules to cell surface receptors to growth factors and enzymes. Despite the diversity of the decorin interacting network, two main roles emerge as prominent themes in decorin function: maintenance of cellular structure and outside-in signaling, culminating in anti-tumorigenic effects. Here we present contemporary knowledge regarding the decorin interacting network and discuss in detail the biological relevance of these pleiotropic interactions, some of which could be targeted by therapeutic interventions.
Topics: Animals; Collagen; Decorin; Extracellular Matrix; Glycosaminoglycans; Humans; Protein Interaction Maps; Proteoglycans; Signal Transduction
PubMed: 27693454
DOI: 10.1016/j.matbio.2016.09.009 -
Advanced Drug Delivery Reviews Feb 2016Decorin is a prototypical small leucine-rich proteoglycan that epitomizes the multifunctional nature of this critical gene family. Soluble decorin engages multiple... (Review)
Review
Decorin is a prototypical small leucine-rich proteoglycan that epitomizes the multifunctional nature of this critical gene family. Soluble decorin engages multiple receptor tyrosine kinases within the target-rich environment of the tumor stroma and tumor parenchyma. Upon receptor binding, decorin initiates signaling pathways within endothelial cells downstream of VEGFR2 that ultimately culminate in a Peg3/Beclin 1/LC3-dependent autophagic program. Concomitant with autophagic induction, decorin blunts capillary morphogenesis and endothelial cell migration, thereby significantly compromising tumor angiogenesis. In parallel within the tumor proper, decorin binds multiple RTKs with high affinity, including Met, for a multitude of oncosuppressive functions including growth inhibition, tumor cell mitophagy, and angiostasis. Decorin is also pro-inflammatory by modulating macrophage function and cytokine secretion. Decorin suppresses tumorigenic growth, angiogenesis, and prevents metastatic lesions in a variety of in vitro and in vivo tumor models. Therefore, decorin would be an ideal therapeutic candidate for combating solid malignancies.
Topics: Animals; Autophagy; Decorin; ErbB Receptors; Genetic Therapy; Humans; Neoplasms; Neovascularization, Pathologic; Proto-Oncogene Proteins c-met
PubMed: 26522384
DOI: 10.1016/j.addr.2015.10.016 -
International Journal of Molecular... Sep 2021Two small leucine-rich proteoglycans (SLRP), decorin and biglycan, play important roles in structural-functional integrity of the placenta and fetal membranes, and their... (Review)
Review
Two small leucine-rich proteoglycans (SLRP), decorin and biglycan, play important roles in structural-functional integrity of the placenta and fetal membranes, and their alterations can result in several pregnancy-associated diseases. In this review, we briefly discuss normal placental structure and functions, define and classify SLRPs, and then focus on two SLRPs, decorin (DCN) and biglycan (BGN). We discuss the consequences of deletions/mutations of DCN and BGN. We then summarize DCN and BGN expression in the pregnant uterus, myometrium, decidua, placenta, and fetal membranes. Actions of these SLRPs as ligands are then discussed in the context of multiple binding partners in the extracellular matrix and cell surface (receptors), as well as their alterations in pathological pregnancies, such as preeclampsia, fetal growth restriction, and preterm premature rupture of membranes. Lastly, we raise some unanswered questions as food for thought.
Topics: Animals; Biglycan; Decorin; Female; Fetal Growth Retardation; Gene Expression Regulation; Humans; Mutation; Placenta; Pre-Eclampsia; Pregnancy
PubMed: 34638928
DOI: 10.3390/ijms221910584