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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 -
Placenta Feb 2020Abnormally invasive placenta (AIP, aka placenta accreta spectrum; PAS) is an increasingly common pregnancy pathology, which, despite significant morbidity risk to the...
INTRODUCTION
Abnormally invasive placenta (AIP, aka placenta accreta spectrum; PAS) is an increasingly common pregnancy pathology, which, despite significant morbidity risk to the mother, is often undiagnosed prior to delivery. We tested several potential biomarkers in plasma from PAS mothers to determine whether any were sufficiently robust for a formal, diagnostic accuracy study.
METHODS
We examined hyperglycosylated hCG (h-hCG), decorin and IL-8, based on biological plausibility and literature indications that they might be altered in PAS. These analytes were assayed by ELISA in maternal plasma from five groups, comprising (1) normal term controls, (2) placenta previa controls, and cases of (3) placenta increta/percreta without placenta previa, (4) placenta previa increta/percreta and (5) placenta previa accreta.
RESULTS
There were no differences in h-hCG, ß-hCG or the h-hCG/ß-hCG ratio between the groups. Mean decorin levels were increased in previa controls (Group 2) compared to the other groups, but there was substantial overlap between the individual values. While an initial multiplex assay showed a greater value for IL-8 in the placenta previa increta/percreta group (Group 4) compared to placenta previa controls (Group 2), the subsequent validation ELISA for IL-8 showed no differences between the groups.
DISCUSSION
We conclude that the absence of differences and the extent of overlap between cases and controls does not justify further assessment of these biomarkers.
Topics: Adult; Biomarkers; Chorionic Gonadotropin; Decorin; Female; Humans; Interleukin-8; Placenta Accreta; Placenta Previa; Pregnancy
PubMed: 32174305
DOI: 10.1016/j.placenta.2020.01.007 -
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 -
Acta Biomaterialia Nov 2023Tissue regeneration/fibrosis after injury is intricately regulated by the immune cascade reaction and extracellular matrix (ECM). Dysregulated cascade signal could...
Tissue regeneration/fibrosis after injury is intricately regulated by the immune cascade reaction and extracellular matrix (ECM). Dysregulated cascade signal could jeopardize tissue homeostasis leading to fibrosis. Bioactive scaffolds mimicking natural ECM microstructure and chemistry could regulate the cascade reaction to achieve tissue regeneration. The current study constructed an ECM-engineered micro/nanofibrous scaffold using self-assembled nanofibrous collagen and decorin (DCN)-loaded microfibers to regulate the immune cascade reaction. The ECM-engineered scaffold promoted anti-inflammatory and pro-regenerative effects, M2 polarization of macrophages, by nanofibrous collagen. The ECM-engineered scaffold could release DCN to inhibit inflammation-associated fibrous angiogenesis. Yet, to prevent excessive M2 activity leading to tissue fibrosis, controlled release of DCN was expected to elicit M1 activity and achieve M1/M2 balance in the repair process. Regulated cascade reaction guided favorable crosstalk between macrophages, endothelial cells and fibroblasts by proximity. Additionally, decorin could also antagonize TGF-β1 via TGF-β/Smad3 pathway to suppress fibrotic activity of fibroblasts. Hence, ECM-engineered scaffolds could exert effective regulation of the immune cascade reaction by microstructure and DCN release and achieve the balance between tissue fibrosis and regeneration. STATEMENT OF SIGNIFICANCE: With the incidence of up to 74.6%, failed back surgery syndrome (FBSS) has been a lingering issue in spine surgery, which poses a heavy socio-economic burden to society. Epidural fibrosis is believed to be responsible for the onset of FBSS. Current biomaterial-based strategies treating epidural fibrosis mainly rely on physical barriers and unidirectional suppression of inflammation. Regulation of the immune cascade reaction for inhibiting fibrosis has not been widely studied. Based on the simultaneous regulation of M1/M2 polarization and intercellular crosstalk, the ECM-engineered micro/nanofibrous scaffolds constructed in the current study could exert an immune cascade effect to coordinate tissue regeneration and inhibit fibrosis. This finding makes a significant contribution in the development of a treatment for epidural fibrosis and FBSS.
Topics: Humans; Tissue Scaffolds; Tissue Engineering; Endothelial Cells; Decorin; Extracellular Matrix; Collagen; Fibrosis; Inflammation
PubMed: 37673231
DOI: 10.1016/j.actbio.2023.08.058 -
Osteoarthritis and Cartilage Aug 2021To delineate the activities of decorin and biglycan in the progression of post-traumatic osteoarthritis (PTOA).
OBJECTIVE
To delineate the activities of decorin and biglycan in the progression of post-traumatic osteoarthritis (PTOA).
DESIGN
Three-month-old inducible biglycan (Bgn) and decorin/biglycan compound (Dcn/Bgn) knockout mice were subjected to the destabilization of the medial meniscus (DMM) surgery to induce PTOA. The OA phenotype was evaluated by assessing joint structure and sulfated glycosaminoglycan (sGAG) staining via histology, surface collagen fibril nanostructure and calcium content via scanning electron microscopy, tissue modulus via atomic force microscopy-nanoindentation, as well as subchondral bone structure and meniscus ossification via micro-computed tomography. Outcomes were compared with previous findings in the inducible decorin (Dcn) knockout mice.
RESULTS
In the DMM model, Bgn mice developed similar degree of OA as the control (0.44 [-0.18 1.05] difference in modified Mankin score), different from the more severe OA phenotype observed in Dcn mice (1.38 [0.91 1.85] difference). Dcn/Bgn mice exhibited similar histological OA phenotype as Dcn mice (1.51 [0.97 2.04] difference vs control), including aggravated loss of sGAGs, salient surface fibrillation and formation of osteophyte. Meanwhile, Dcn/Bgn mice showed further cartilage thinning than Dcn mice, resulting in the exposure of underlying calcified tissues and aberrantly high surface modulus. Bgn and Dcn/Bgn mice developed altered subchondral trabecular bone structure in both Sham and DMM groups, while Dcn and control mice did not.
CONCLUSION
In PTOA, decorin plays a more crucial role than biglycan in regulating cartilage degeneration, while biglycan is more important in regulating subchondral bone structure. The two have distinct activities and modest synergy in the pathogenesis of PTOA.
Topics: Animals; Biglycan; Cancellous Bone; Cartilage, Articular; Decorin; Disease Models, Animal; Disease Progression; Menisci, Tibial; Mice, Knockout; Ossification, Heterotopic; Osteoarthritis; Osteophyte; Tibial Meniscus Injuries; Mice
PubMed: 33915295
DOI: 10.1016/j.joca.2021.03.019 -
Seminars in Cancer Biology May 2020The need for more effective cancer therapies is omnipresent as the ever-complex, and highly adaptive, mechanisms of tumor biology allow this disease to elude even the... (Review)
Review
The need for more effective cancer therapies is omnipresent as the ever-complex, and highly adaptive, mechanisms of tumor biology allow this disease to elude even the most stringent treatment options. The expanding field of proteoglycan signaling is enticing as a reservoir of potential drug targets and prospects for novel therapeutic strategies. The newest trend in proteoglycan biology is the interplay between extracellular signaling and autophagy fueled by the close link between autophagy and angiogenesis. Here we summarize the most current evidence surrounding proteoglycan signaling in both of these biological processes featuring the well-known suspects, decorin and perlecan, as well as other up-and-coming neophytes in this evolving signaling web.
Topics: Animals; Autophagy; Biomarkers; Decorin; Endothelial Cells; Humans; Neovascularization, Pathologic; Proteoglycans; Signal Transduction
PubMed: 31078640
DOI: 10.1016/j.semcancer.2019.05.003 -
Medical Hypotheses Jul 2021Coronavirus pandemic has emerged as an extraordinary healthcare crisis in modern times. The SARS-CoV-2 novel coronavirus has high transmission rate, is more aggressive...
Coronavirus pandemic has emerged as an extraordinary healthcare crisis in modern times. The SARS-CoV-2 novel coronavirus has high transmission rate, is more aggressive and virulent in comparison to previously known coronaviruses. It primarily attacks the respiratory system by inducing cytokine storm that causes systemic inflammation and pulmonary fibrosis. Decorin is a pluripotent molecule belonging to a leucine rich proteoglycan group that exerts critical role in extracellular matrix (ECM) assembly and regulates cell growth, adhesion, proliferation, inflammation, and fibrogenesis. Interestingly, decorin has potent anti-inflammatory, cytokine inhibitory, and anti-fibrillogenesis effects which make it a potential drug candidate against the COVID-19 related complications especially in the context of lung fibrosis. Herein, we postulate that owing to its distinctive pharmacological actions and immunomodulatory effect, decorin can be a promising preclinical therapeutic agent for the therapy of COVID-19.
Topics: COVID-19; Cytokines; Decorin; Humans; Pandemics; SARS-CoV-2
PubMed: 34098463
DOI: 10.1016/j.mehy.2021.110612 -
Free Radical Research Dec 2018Decorin (DCN) is a proteoglycan constituent of the extracellular matrix (ECM) possessing powerful antifibrotic, anti-inflammation, antioxidant, and antiangiogenic... (Review)
Review
Decorin (DCN) is a proteoglycan constituent of the extracellular matrix (ECM) possessing powerful antifibrotic, anti-inflammation, antioxidant, and antiangiogenic properties. By attaching to receptors in the cell surface or to several ECM molecules, it regulates plenty of cellular functions, consequently influencing cell differentiation, proliferation, and apoptosis. These processes are dependent on cell types, biological contexts, and interfere with pathological processes such as cardiovascular diseases. In this review, we briefly discuss the potential of DCN targeting in addressing cardiovascular diseases (CVD). We dive into its interactome and discuss how its interaction with the proteins can affect disease progression, and how DCN can be a possible target for CVD therapeutics.
Topics: Animals; Cardiovascular Diseases; Decorin; Humans; Molecular Targeted Therapy
PubMed: 30468093
DOI: 10.1080/10715762.2018.1516285 -
The Journal of Histochemistry and... Apr 2018It is now well-established that members of the small leucine-rich proteoglycan (SLRP) family act in their soluble form, released proteolytically from the extracellular... (Review)
Review
It is now well-established that members of the small leucine-rich proteoglycan (SLRP) family act in their soluble form, released proteolytically from the extracellular matrix (ECM), as danger-associated molecular patterns (DAMPs). By interacting with Toll-like receptors (TLRs) and the inflammasome, the two SLRPs, biglycan and decorin, autonomously trigger sterile inflammation. Recent data indicate that these SLRPs, besides their conventional role as pro-inflammatory DAMPs, additionally trigger anti-inflammatory signaling pathways to tightly control inflammation. This is brought about by selective employment of TLRs, their co-receptors, various adaptor molecules, and through crosstalk between SLRP-, reactive oxygen species (ROS)-, and sphingolipid-signaling. In this review, the complexity of SLRP signaling in immune and kidney resident cells and its relevance for renal inflammation is discussed. We propose that the dichotomy in SLRP signaling (pro- and anti-inflammatory) allows for fine-tuning the inflammatory response, which is decisive for the outcome of inflammatory kidney diseases.
Topics: Animals; Autophagy; Biglycan; Decorin; Fibrosis; Humans; Immunity, Innate; Inflammasomes; Inflammation; Kidney; Kidney Diseases; Signal Transduction; Small Leucine-Rich Proteoglycans; Transforming Growth Factor beta
PubMed: 29290137
DOI: 10.1369/0022155417738752 -
Journal of Dental Research Nov 2017Previous studies demonstrated that chondroitin sulfate proteoglycans (CSPGs) on apical surfaces of palatal medial edge epithelial (MEE) cells were necessary for palatal...
Previous studies demonstrated that chondroitin sulfate proteoglycans (CSPGs) on apical surfaces of palatal medial edge epithelial (MEE) cells were necessary for palatal adhesion. In this study, we identified 2 proteoglycans, biglycan and decorin, that were expressed in the palatal shelves prior to adhesion. In addition, we established that these proteoglycans were dependent on transforming growth factor β (TGFβ) signaling. Laser capture microdissection was used to collect selected palatal epithelial cells from embryonic mouse embryos at various palate development stages. The expression of specific messenger RNA (mRNA) for biglycan and decorin was determined with quantitative real-time polymerase chain reaction. The TGFβrI kinase inhibitor (SB431542) was used in palatal organ cultures to determine if blocking TFGβ signaling changed biglycan and decorin distribution. Immunohistochemistry of both biglycan and decorin revealed expression on the apical and lateral surfaces of MEE cells. Biglycan protein and mRNA levels peaked as the palatal shelves adhered. Decorin was less abundant on the apical epithelial surface and also had reduced mRNA levels compared to biglycan. Their proteins were not expressed on MEE cells of palates treated with SB431542, an inhibitor of TGFβ signaling. The temporal expression of biglycan and decorin on the apical surface of MEE, combined with the evidence that these proteins were regulated through the TGFβ pathway, indicated that they may be important for adhesion.
Topics: Animals; Benzamides; Biglycan; Cell Adhesion; Decorin; Dioxoles; Immunohistochemistry; Laser Capture Microdissection; Mice; Palate; RNA, Messenger; Real-Time Polymerase Chain Reaction; Signal Transduction; Transforming Growth Factor beta
PubMed: 28759311
DOI: 10.1177/0022034517722783