-
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 -
Ginekologia Polska 2020Preeclampsia (PE) is a pregnancy complication caused by typically limited proliferation, apoptosis, migration, and invasion of extra-trophoblast cells. Decorin (DCN) is...
OBJECTIVES
Preeclampsia (PE) is a pregnancy complication caused by typically limited proliferation, apoptosis, migration, and invasion of extra-trophoblast cells. Decorin (DCN) is a decidua-derived transforming growth factor (TGF)-binding proteoglycan which exerts multiple physiological functions such as collagen fibrillogenesis, myogenesis, angiostasis, and restraining placental invasiveness by adversely regulate proliferation, migration, and invasiveness of human extravillous trophoblast cells. Preeclampsia is mainly classified as early- and late-onset PE according to the timing of the disease onset. In the present study, we aimed to investigate the DCN levels in early-onset PE (EOPE, < 34 weeks) and late-onset severe PE (LOPE, ≥ 34 weeks) and uncomplicated pregnancies.
MATERIAL AND METHODS
In this case-control study, serum samples were obtained from 21 pregnant women with EOPE and 29 pregnant women with LOPE, as well as from 38 healthy controls (n = 12 early-onset controls and n = 26 late-onset controls) with uncomplicated pregnancies.
RESULTS
The mean DCN level was statistically significantly higher in the early-onset PE controls than late-onset PE controls (p = 0.040). Although the mean DCN level was higher in the early-onset PE controls than EOPE and LOPE groups, it did not reach statistical significance (p = 0.119 and p = 0.117, respectively).
CONCLUSIONS
Although DCN has been thought to play a role in the pathophysiology of PE, our study results show that DCN is not a useful predictive marker of EOPE and LOPE. Further large-scale studies are needed to draw a definitive conclusion.
Topics: Adolescent; Adult; Biomarkers; Case-Control Studies; Decorin; Female; Humans; Pre-Eclampsia; Predictive Value of Tests; Pregnancy; Pregnancy Trimesters; Prenatal Diagnosis; Prospective Studies; Young Adult
PubMed: 32495932
DOI: 10.5603/GP.2020.0050 -
Biochimica Et Biophysica Acta. Reviews... Jan 2024Asporin (ASPN) has been identified as one of the members of the class I small leucine-rich proteoglycans (SLRPs) family in the extracellular matrix (ECM). It is involved... (Review)
Review
Asporin (ASPN) has been identified as one of the members of the class I small leucine-rich proteoglycans (SLRPs) family in the extracellular matrix (ECM). It is involved in classic ensigns of cancers such as self-dependent growth, resistance to growth inhibitors, restricting apoptosis, cancer metastasis, and bone-related disorders. ASPN is different from other members of SLRPs, such as decorin (DCN) and biglycan (BGN), in a way that it contains a distinctive length of aspartate (D) residues in the amino (N) -terminal region. These D-repeats residues possess germline polymorphisms and are identified to be linked with cancer progression and osteoarthritis (OA). The polyaspartate stretch in the N-terminal region of the protein and its resemblance to DCN are the reasons it is called asporin. In this review, we comprehensively summarized and updated the dual role of ASPN in various malignancies, its structure in mice and humans, variants, mutations, cancer-associated signalings and functions, the relationship between ASPN and cancer-epithelial, stromal fibroblast crosstalk, immune cells and immunosuppression in cancer and other diseases. In cancer and other bone-related diseases, ASPN is identified to be regulating various signaling pathways such as TGFβ, Wnt/β-catenin, notch, hedgehog, EGFR, HER2, and CD44-mediated Rac1. These pathways promote cancer cell invasion, proliferation, and migration by mediating the epithelial-to-mesenchymal transition (EMT) process. Finally, we discussed mouse models mimicking ASPN in vivo function in cancers and the probability of therapeutic targeting of ASPN in cancer cells, fibrosis, and other bone-related diseases.
Topics: Humans; Animals; Mice; Extracellular Matrix Proteins; Extracellular Matrix; Neoplasms; Signal Transduction; Transforming Growth Factor beta
PubMed: 38008263
DOI: 10.1016/j.bbcan.2023.189029 -
International Journal of Biological... Oct 2022Scars occur as a result of fibrosis after tissue damage or surgery and reports suggest that excessive Transforming growth factor-β (TGF-β) activity during the process...
Scars occur as a result of fibrosis after tissue damage or surgery and reports suggest that excessive Transforming growth factor-β (TGF-β) activity during the process of wound healing leads to progressive fibrosis. Decorin is an extracellular matrix (ECM) protein which regulates collagen fibrillogenesis. However, targeted delivery and effective protein therapy remains a challenge owing to degradation byproteases. Hence, we aimed to deliver Decorin in a sustainable mode for the reduction of TGF-β levels and subsequent scar formation. Herein, we have fabricated PCL-Gelatin bio-mimetic scaffolds to optimize the bio-activity and provide localized delivery of recombinant Decorin. The degradation and drug release patterns reveals that this biomaterial is biodegradable and offers sustained release of the recombinant Decorin. Decorin loaded nanofiber displayed lower adhesion and proliferation rates in in-vitro conditions. Moreover, Decorin loaded scaffolds demonstrated morphological changes in cells, specifically targeting the myofibroblast. The expression of TGF-β was also scrutinized to understand the effect of Decorin loaded nanofibers. Besides, in the in-vitro fibrotic model, Decorin loaded nanofibers efficiently reduced the expression of ECM related proteins. Therefore, we report the sustained delivery of the recombinant Decorin from nanofiber dressing to potentially obstruct scar formation during the process of wound healing.
Topics: Biocompatible Materials; Biomimetics; Cicatrix; Collagen; Decorin; Delayed-Action Preparations; Extracellular Matrix Proteins; Fibrosis; Gelatin; Humans; Transforming Growth Factor beta; Transforming Growth Factor beta1; Transforming Growth Factors
PubMed: 35952816
DOI: 10.1016/j.ijbiomac.2022.08.029 -
Journal of Gynecology Obstetrics and... Dec 2021Decorin is a leucine-rich proteoglycan, affects the proliferation, migration, and invasion of extravillous trophoblasts (EVTs). In this study, we aimed to determine the...
OBJECTIVE
Decorin is a leucine-rich proteoglycan, affects the proliferation, migration, and invasion of extravillous trophoblasts (EVTs). In this study, we aimed to determine the localization of decorin in the implantation site in human tubal ectopic pregnancy, to compare decorin expression levels in ectopic and intrauterine pregnancy, and to investigate the relationship between implantation depth of the tubal wall and expression levels of decorin.
METHODS
15 patients underwent salpingectomy for tubal ectopic pregnancy and 15 underwent curettage for voluntary interruption of pregnancy were included. All blocks were stained with decorin immunohistochemical staining. Trophoblastic cells of tubal Stage I-III and tubal epithelial and stromal cells were analyzed in terms of presence and intensity of decorin staining.
RESULTS
Decorin was expressed in both tubal and intrauterine trophoblasts, stroma, and surface epithelium during the first trimester of pregnancy. Decorin staining intensity was significantly lower in the villous cytotrophoblasts and syncytiotrophoblasts in tubal ectopic pregnancies, compared to intrauterine pregnancies (p = 0.001 for both). Decorin staining intensity also significantly lower in the extravillous cytotrophoblasts and syncytiotrophoblasts in the tubal ectopic pregnancies (p = 0.002 and p = 0.001, respectively). There was no significant difference in the staining intensity of the trophoblasts and surface epithelial between Stage II and Stage III tubal invasion; however, the decorin expression was lower in the stroma in Stage III (p = 0.094).
CONCLUSION
Decorin expression is significantly lower in trophoblastic cells of tubal ectopic pregnancies than the intrauterine pregnancies. Although it remains limited to explain the underlying cellular mechanisms, decorin seems to play a role in the development of tubal pregnancy.
Topics: Adult; Case-Control Studies; Decorin; Female; Gene Expression; Humans; Pregnancy; Pregnancy, Ectopic; Trophoblasts
PubMed: 34469778
DOI: 10.1016/j.jogoh.2021.102213 -
Frontiers in Pharmacology 2019Healing of cutaneous wounds is a complex and well-coordinated process requiring cooperation among multiple cells from different lineages and delicately orchestrated... (Review)
Review
Healing of cutaneous wounds is a complex and well-coordinated process requiring cooperation among multiple cells from different lineages and delicately orchestrated signaling transduction of a diversity of growth factors, cytokines, and extracellular matrix (ECM) at the wound site. Most skin wound healing in adults is imperfect, characterized by scar formation which results in significant functional and psychological sequelae. Thus, the reconstruction of the damaged skin to its original state is of concern to doctors and scientists. Beyond the traditional treatments such as corticosteroid injection and radiation therapy, several growth factors or cytokines-based anti-scarring products are being or have been tested in clinical trials to optimize skin wound healing. Unfortunately, all have been unsatisfactory to date. Currently, accumulating evidence suggests that the ECM not only functions as the structural component of the tissue but also actively modulates signal transduction and regulates cellular behaviors, and thus, ECM should be considered as an alternative target for wound management pharmacotherapy. Of particular interest are small leucine-rich proteoglycans (SLRPs), a group of the ECM, which exist in a wide range of connecting tissues, including the skin. This manuscript summarizes the most current knowledge of SLRPs regarding their spatial-temporal expression in the skin, as well as lessons learned from the genetically modified animal models simulating human skin pathologies. In this review, particular focus is given on the diverse roles of SLRP in skin wound healing, such as anti-inflammation, pro-angiogenesis, pro-migration, pro-contraction, and orchestrate transforming growth factor (TGF)β signal transduction, since cumulative investigations have indicated their therapeutic potential on reducing scar formation in cutaneous wounds. By conducting this review, we intend to gain insight into the potential application of SLRPs in cutaneous wound healing management which may pave the way for the development of a new generation of pharmaceuticals to benefit the patients suffering from skin wounds and their sequelae.
PubMed: 32063855
DOI: 10.3389/fphar.2019.01649 -
Plastic and Reconstructive Surgery.... Apr 2022Variations in skin healing capacities are observed during different murine embryonic developmental stages. Through embryonic day 16 (E16), embryos are able to regenerate...
BACKGROUND
Variations in skin healing capacities are observed during different murine embryonic developmental stages. Through embryonic day 16 (E16), embryos are able to regenerate dermal architecture following flank skin wounding; however, after E17, wounds heal incompletely, inducing scar formation. The regenerative ability of the E16 fetal dermis depends on the migration of dermal mesenchymal cells. Decorin is a small molecule known to affect tissue tensile strength, cell phenotype, and tissue repair, including skin wound healing. In the current study, we evaluated the expression and roles of decorin in wound healing.
METHODS
Surgical injury was induced at E16 and E17 in ICR mouse embryos. Decorin expression was evaluated in tissue samples from these embryos using immunohistochemistry and reverse transcription quantitative polymerase chain reaction. Cell migration assays were used to evaluate wound healing capability of separated dermal and fascial tissues.
RESULTS
Our results showed that decorin exhibited distinct expression patterns during wound healing at E16 versus E17. Additionally, decorin expression altered cell migration in vitro. Dermal and fascial mesenchymal cells were found to exhibit distinct migration patterns concomitant with altered decorin expression. Specifically, decorin inhibited migration and favored scar formation.
CONCLUSION
Decorin expression may contribute to scar formation in the late stage of mouse embryos by inhibiting the migration of dermal mesenchymal cells.
PubMed: 35425688
DOI: 10.1097/GOX.0000000000004245 -
Reproductive Sciences (Thousand Oaks,... Jan 2021Preterm birth is a leading cause of infant morbidity and mortality. Decorin and biglycan are proteoglycans that play key roles in maintaining the connective tissue...
Preterm birth is a leading cause of infant morbidity and mortality. Decorin and biglycan are proteoglycans that play key roles in maintaining the connective tissue matrix and tensile strength of human fetal membranes and have been previously linked to PPROM. Extracellular matrix proteins, such as matrix metalloproteinase 2 (MMP-2), matrix metalloproteinase 9 (MMP-9), TIMP metallopeptidase inhibitor 1 (TIMP-1), TIMP metallopeptidase inhibitor 2 (TIMP-2), and collagen VI (COL-6), have also been linked to PPROM and may have utility in a serum-based screening model for this condition. To define the natural course of serum decorin and biglycan expression throughout the duration of healthy pregnancy, to explore patterns of serum decorin and biglycan expression in serum of asymptomatic women who go on to develop spontaneous preterm labor, and to investigate the potential role for matrix metalloproteinases, their inhibitors, and collagen VI in a serum-based screening model to predict PPROM. Serum decorin level decreases less than 1% per week, and serum biglycan decreases by 2.9% per week over the duration of healthy pregnancy. Serum decorin and biglycan concentrations do not differ in spontaneous preterm labor cases compared with those in controls. Mean concentrations of MMP-2, MMP-9, TIMP-1, TIMP-2, and COL-6 do not differ in PPROM cases compared with those in controls. We have demonstrated that serum decorin and biglycan concentrations remain stable throughout the duration of normal pregnancy and are not early indicators of preterm labor, while common MMPs, TIMPs, and collagen VI are not early indicators of PPROM.
Topics: Biglycan; Biomarkers; Collagen Type VI; Decorin; Enzyme-Linked Immunosorbent Assay; Extracellular Matrix Proteins; Female; Fetal Membranes, Premature Rupture; Humans; Matrix Metalloproteinases; Predictive Value of Tests; Pregnancy; Premature Birth; Retrospective Studies; Tissue Inhibitor of Metalloproteinases
PubMed: 32804350
DOI: 10.1007/s43032-020-00251-1 -
Journal of Orthopaedic Research :... Oct 2023The small leucine-rich proteoglycans, decorin and biglycan, are minor components of the tendon extracellular matrix that regulate fibrillogenesis and matrix assembly....
The small leucine-rich proteoglycans, decorin and biglycan, are minor components of the tendon extracellular matrix that regulate fibrillogenesis and matrix assembly. Our study objective was to define the temporal roles of decorin and biglycan during tendon healing using inducible knockout mice to include genetic knockdown at specific phases of healing: time of injury, the proliferative phase, and the remodeling phase. We hypothesized that knockdown of decorin or biglycan would adversely affect tendon healing, and that by prescribing the timing of knockdown, we could elucidate the temporal roles of these proteins during healing. Contrary to our hypothesis, decorin knockdown did not affect tendon healing. However, when biglycan was knocked down, either alone or coupled with decorin, tendon modulus was increased relative to wild-type mice, and this finding was consistent among all induction timepoints. At 6 weeks postinjury, we observed increased expression of genes associated with the extracellular matrix and growth factor signaling in the biglycan knockdown and compound decorin-biglycan knockdown tendons. Interestingly, these groups demonstrated opposing trends in gene expression as a function of knockdown-induction timepoint, highlighting distinct temporal roles for decorin and biglycan. In summary, this study finds that biglycan plays multiple functions throughout tendon healing, with the most impactful, detrimental role likely occurring during late-stage healing. Statement of clinical importance: This study helps to define the molecular factors that regulate tendon healing, which may aid in the development of new clinical therapies.
Topics: Animals; Mice; Biglycan; Decorin; Extracellular Matrix Proteins; Mice, Knockout; Tendons; Wound Healing
PubMed: 37132501
DOI: 10.1002/jor.25590 -
Frontiers in Oncology 2019The small leucine-rich proteoglycan (SLRP) family consists of 18 members categorized into five distinct classes, the traditional classes I-III, and the non-canonical... (Review)
Review
The small leucine-rich proteoglycan (SLRP) family consists of 18 members categorized into five distinct classes, the traditional classes I-III, and the non-canonical classes IV-V. Unlike the other class I SLRPs (decorin and biglycan), asporin contains a unique and conserved stretch of aspartate (D) residues in its N terminus, and germline polymorphisms in the D-repeat-length are associated with osteoarthritis and prostate cancer progression. Since the first discovery of asporin in 2001, previous studies have focused mainly on its roles in bone and joint diseases, including osteoarthritis, intervertebral disc degeneration and periodontal ligament mineralization. Recently, gene expression was also reported to be dysregulated in tumor tissues of different types of cancer, and to act as oncogene in pancreatic, colorectal, gastric, and prostate cancers, and some types of breast cancer, though it is also reported to function as a tumor suppressor gene in triple-negative breast cancer. Furthermore, asporin is also positively or negatively correlated with tumor proliferation, migration, invasion, and patient prognosis through its regulation of different signaling pathways, including the TGF-β, EGFR, and CD44 pathways. In this review, we seek to elucidate the signaling pathways and functions regulated by asporin in different types of cancer and to highlight some important issues that require investigation in future research.
PubMed: 31608236
DOI: 10.3389/fonc.2019.00948