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Clinical and Translational Medicine May 2024Human dermal fibroblasts (HDFs) are essential in the processes of skin ageing and wound healing. However, the underlying mechanism of HDFs in skin healing of the elderly...
BACKGROUND
Human dermal fibroblasts (HDFs) are essential in the processes of skin ageing and wound healing. However, the underlying mechanism of HDFs in skin healing of the elderly has not been well defined. This study aims to elucidate the mechanisms of HDFs senescence and how senescent HDFs affect wound healing in aged skin.
METHODS
The expression and function of sperm equatorial segment protein 1 (SPESP1) in skin ageing were evaluated via in vivo and in vitro experiments. To delve into the potential molecular mechanisms by which SPESP1 influences skin ageing, a combination of techniques was employed, including proteomics, RNA sequencing, immunoprecipitation, chromatin immunoprecipitation and liquid chromatography-mass spectrometry analyses. Clearance of senescent cells by dasatinib plus quercetin (D+Q) was investigated to explore the role of SPESP1-induced senescent HDFs in wound healing.
RESULTS
Here, we define the critical role of SPESP1 in ameliorating HDFs senescence and retarding the skin ageing process. Mechanistic studies demonstrate that SPESP1 directly binds to methyl-binding protein, leading to Decorin demethylation and subsequently upregulation of its expression. Moreover, SPESP1 knockdown delays wound healing in young mice and SPESP1 overexpression induces wound healing in old mice. Notably, pharmacogenetic clearance of senescent cells by D+Q improved wound healing in SPESP1 knockdown skin.
CONCLUSIONS
Taken together, these findings reveal the critical role of SPESP1 in skin ageing and wound healing, expecting to facilitate the development of anti-ageing strategies and improve wound healing in the elderly.
Topics: Animals; Humans; Male; Mice; Cellular Senescence; Down-Regulation; Fibroblasts; Quercetin; Skin Aging; Wound Healing; Carrier Proteins; Seminal Plasma Proteins
PubMed: 38764260
DOI: 10.1002/ctm2.1660 -
Alternative Therapies in Health and... Oct 2023This study aims to investigate the role of decorin in the adhesion process of Treponema pallidum subspecies pallidum (T. pallidum) to human brain microvascular...
OBJECTIVE
This study aims to investigate the role of decorin in the adhesion process of Treponema pallidum subspecies pallidum (T. pallidum) to human brain microvascular endothelial cells.
METHODS
The study involved an in vitro experimental design. Western blot analysis was conducted to determine the protein expression level of decorin in the cells. The cells were divided into four groups: Tp group, inactivated Tp group, LPS group, and negative control group. The adhesion of T. pallidum to the cells was analyzed using darkfield microscopy counting and quantitative polymerase chain reaction (qPCR). The cells were divided into four groups based on different preprocessing treatments: control group, decorin group, DCN-siRNA group, and DCN-siRNA+decorin group. Changes in the F-actin of the cells were explored using confocal laser scanning microscopy. The cells were divided into the Tp group, Tp+decorin group, and control group.
RESULTS
Western blot analysis showed high expression of decorin in the Tp group and LPS group. Darkfield microscopy counting revealed a significantly higher number of T. pallidum adhered to a single cell in the decorin group compared to the control group. Conversely, the number of adhered T. pallidum was significantly lower in the DCN-siRNA group compared to the control group. qPCR results indicated a considerably higher T. pallidum load in the decorin group compared to the control group. In the Tp group, T. pallidum treatment induced the reorganization of F-actin, while the distribution of F-actin in the Tp+decorin group was comparable to that of the control group.
CONCLUSIONS
Decorin enhances the adhesion of T. pallidum to human brain microvascular endothelial cells, suggesting that decorin may act as one of the receptors regulating the adhesion of T. pallidum to cells. Furthermore, T. pallidum treatment triggers the rearrangement of F-actin in cells, and decorin plays a protective role in this process.
Topics: Humans; Treponema pallidum; Decorin; Endothelial Cells; Actins; Globus Pallidus; Lipopolysaccharides
PubMed: 37471666
DOI: No ID Found -
Clinical Rheumatology Dec 2023This study investigated the efficacy of sericin in treating experimental Achilles tendinopathy (AT) in rats via the transforming growth factor-beta (TGF-β)/mothers...
OBJECTIVE
This study investigated the efficacy of sericin in treating experimental Achilles tendinopathy (AT) in rats via the transforming growth factor-beta (TGF-β)/mothers against decapentaplegic (Smad) pathway compared with diclofenac sodium (DS).
METHOD
An AT model was induced in rats using collagenase enzyme type I and divided into 5 groups: C (control), AT (diseased control), ATS (AT treated with sericin), ATN (AT treated with DS), and ATSN (AT treated with sericin and DS). Sericin injection was given on the 3 and 6 days by intratendinous injection (0.8 g/kg/mL), and DS was administered for 14 days by oral gavage (1.1 mg/kg/day). Serum concentrations of total oxidant-antioxidant status (TOS-TAS), TGF-β1, decorin, Smad2, and connective tissue growth factor (CTGF) were measured. Histopathologic and immunohistochemical (IHC) studies were conducted on Achilles tendon samples.
RESULTS
The TOS, oxidative stress index (OSI), TGF-β1, Smad2, CTGF, and decorin serum concentrations were significantly higher in AT than in C and significantly lower in ATS than in AT (P<0.05). Histopathological examination revealed that irregular fibers, degeneration, and round cell nuclei were significantly elevated in AT. Spindle-shaped fibers were similar to those in C, and degeneration was reduced in ATS. TGF-β1 and Smad2/3 expression was increased, and collagen type I alpha-1 (Col1A1) expression was decreased in AT vs. C (P=0.001). In the ATS, TGF-β1 and Smad2/3 expression decreased, and Col1A1 expression increased. The Bonar score significantly increased in the AT group (P =0.001) and significantly decreased in the ATS group (P =0.027).
CONCLUSION
Sericin shows potential efficacy in reducing oxidative stress and modulating the TGF-β/Smad pathway in experimental AT models in rats. It may be a promising therapeutic agent for AT, warranting further clinical studies for validation. Key Points • This study revealed that sericin mitigates AT-induced damage through the TGF-β/Smad pathway in an AT rat model. • ELISA and IHC investigations corroborated the effectiveness of sericin via the pivotal TGF-β/Smad pathway in tissue repair. • Evidence indicates that sericin enhances collagen synthesis,shapes tendon fiber structure, and diminishes histopathological degeneration. • Sericin's antioxidant properties were reaffirmed in its AT treatment application.
Topics: Rats; Animals; Transforming Growth Factor beta1; Achilles Tendon; Sericins; Decorin; Antioxidants; Tendinopathy; Transforming Growth Factor beta
PubMed: 37733079
DOI: 10.1007/s10067-023-06767-6 -
International Journal of Molecular... Jul 2023Lesions in the human anterior cruciate ligament (ACL) are frequent, unsolved clinical issues due to the limited self-healing ability of the ACL and lack of treatments...
Lesions in the human anterior cruciate ligament (ACL) are frequent, unsolved clinical issues due to the limited self-healing ability of the ACL and lack of treatments supporting full, durable ACL repair. Gene therapy guided through the use of biomaterials may steadily activate the processes of repair in sites of ACL injury. The goal of the present study was to test the hypothesis that functionalized poly(sodium styrene sulfonate)-grafted poly(ε-caprolactone) (pNaSS-grafted PCL) films can effectively deliver recombinant adeno-associated virus (rAAV) vectors as a means of overexpressing two reparative factors (transforming growth factor beta-TGF-β and basic fibroblast growth factor-FGF-2) in primary human ACL fibroblasts. Effective, durable rAAV reporter red fluorescent protein and candidate TGF-β and FGF-2 gene overexpression was achieved in the cells for at least 21 days, especially when pNaSS-grafted PCL films were used versus control conditions, such as ungrafted films and systems lacking vectors or films (between 1.8- and 5.2-fold differences), showing interactive regulation of growth factor production. The expression of TGF-β and FGF-2 from rAAV via PCL films safely enhanced extracellular matrix depositions of type-I/-III collagen, proteoglycans/decorin, and tenascin-C (between 1.4- and 4.5-fold differences) in the cells over time with increased levels of expression of the specific transcription factors Mohawk and scleraxis (between 1.7- and 3.7-fold differences) and without the activation of the inflammatory mediators IL-1β and TNF-α, most particularly with pNaSS-grafted PCL films relative to the controls. This work shows the value of combining rAAV gene therapy with functionalized PCL films to enhance ACL repair.
Topics: Humans; Transforming Growth Factor beta; Dependovirus; Anterior Cruciate Ligament; Fibroblast Growth Factor 2; Fibroblasts
PubMed: 37446318
DOI: 10.3390/ijms241311140 -
Wound Repair and Regeneration :... 2024Hypertrophic scars (HTS) develop from an excessive synthesis of structural proteins like collagen and a decreased expression of proteoglycans such as decorin. Previous...
Hypertrophic scars (HTS) develop from an excessive synthesis of structural proteins like collagen and a decreased expression of proteoglycans such as decorin. Previous research has demonstrated that decorin expression is significantly down-regulated in HTS, deep dermal tissue, and thermally injured tissue, reducing its ability to regulate pro-fibrotic transforming growth factor-beta 1 (TGF-β1) and normal fibrillogenesis. However, treatment of HTS fibroblasts with interferon-alpha 2b (IFN-α2b) has been shown to reduce excessive collagen synthesis and improve HTS by reducing serum TGF-β1 levels. The expression of decorin isoforms in HTS is currently unknown and the effects of TGF-β1 and IFN-α2b on decorin, decorin isoform expression and type 1 collagen are of great interest to our group. Dermal fibroblasts were treated with TGF-β1 and/or IFN-α2b, for 48 h. The expression and secretion of decorin, decorin isoforms and type 1 collagen were quantified with reverse transcription-quantitative polymerase chain reaction, immunofluorescence staining and enzyme-linked immunosorbent assays. The mRNA expression of decorin and each isoform was significantly reduced in HTS fibroblasts relative to normal skin. TGF-β1 decreased the mRNA expression of decorin and decorin isoforms, whereas IFN-α2b showed the opposite effect. IFN-α2b significantly inhibited TGF-β1's effect on the mRNA expression of type I collagen alpha 1 in papillary dermal fibroblasts and overall showed relative effects of inhibiting TGF-β1. These data support that a further investigation into the structural and functional roles of decorin isoforms in HTS pathogenesis is warranted and that IFN-α2b is an important agent in reducing fibrotic outcomes.
Topics: Humans; Cells, Cultured; Cicatrix, Hypertrophic; Collagen; Collagen Type I; Decorin; Fibroblasts; Interferon alpha-2; Interferon-alpha; Protein Isoforms; RNA, Messenger; Transforming Growth Factor beta1; Wound Healing
PubMed: 38243615
DOI: 10.1111/wrr.13155 -
Journal of Clinical Medicine Apr 2024The etiopathogenesis of ACL rupture is not clarified. The aim of this study is to identify genomic regions and genetic variants relevant to anterior cruciate ligament... (Review)
Review
BACKGROUND
The etiopathogenesis of ACL rupture is not clarified. The aim of this study is to identify genomic regions and genetic variants relevant to anterior cruciate ligament injury susceptibility that could be involved in non-contact anterior cruciate ligament ruptures.
METHODS
A systematic review of the literature was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines with a PRISMA checklist and algorithm. A search of PubMed, MEDLINE, CINAHL, Cochrane, EMBASE, and Google Scholar databases was conducted using combinations of the terms "anterior cruciate ligament", "ACL", "rupture", "genetics", "single nucleotide polymorphisms", and "SNP" since the inception of the databases until 2021.
RESULTS
Twenty-three studies were included. A total of 7724 patients were analyzed. In total, 3477 patients had ACL ruptures and 4247 patients were controls. Genetic variants in genes encoding for collagens, elastin, fibrillin, matrix metalloproteinases, proteoglycans, angiogenesis-associated signaling cascade proteins, growth differentiation factors, tissue inhibitors of metalloproteases, interleukins, and fibrinogen were analyzed.
CONCLUSION
Findings regarding the association between genes encoding for collagen (COL3A1, COL1A1, and COL12A1), aggrecan (ACAN), decorin (DCN), matrix metalloproteinase (MMP3), interleukin 6 (IL-6), vascular endothelial growth factor A (VEGFA), biglycan (BGN), fibrinogen (FGB), and ACL injuries were found to be inconclusive. Additional evidence is required in order to establish substantial conclusions regarding the association between genetic variants and ACL rupture.
PubMed: 38673603
DOI: 10.3390/jcm13082330 -
Ultrastructural Pathology Nov 2023Thin endometrium, defined as an endometrial thickness of less than 7 mm during the late follicular phase, is a common cause of frequent cancelation of embryo transfers...
Thin endometrium, defined as an endometrial thickness of less than 7 mm during the late follicular phase, is a common cause of frequent cancelation of embryo transfers or recurrent implantation failure during assisted reproductive treatment. Small proteoglycans regulate intracellular signaling cascades by bridging other matrix molecules and tissue elements, affecting cell proliferation, adhesion, migration, and cytokine concentration. The aim of the study is to investigate the role of small leucine-rich proteoglycans in the pathogenesis of thin and thick human endometrium and their differences from normal endometrium in terms of fine structure properties. Normal, thin, and thick endometrial samples were collected, and small leucine-rich proteoglycans (SLRPs), decorin, lumican, biglycan, and fibromodulin immunoreactivities were comparatively analyzed immunohistochemically. The data were compared statistically. Moreover, ultrastructural differences among the groups were evaluated by transmission electron microscopy. The immunoreactivities of decorin, lumican, and biglycan were higher in the thin endometrial glandular epithelium and stroma compared to the normal and thick endometrium ( < .001). Fibromodulin immunoreactivity was also higher in the thin endometrial glandular epithelium than in the normal and thick endometrium ( < .001). However, there was no statistical difference in the stroma among the groups. Ultrastructural features were not profoundly different among cases. Telocytes, however, were not seen in the thin endometrium in contrast to normal and thin endometrial tissues. These findings suggest a possible role of changes in proteoglycan levels in the pathogenesis of thin endometrium.
Topics: Female; Humans; Biglycan; Small Leucine-Rich Proteoglycans; Lumican; Decorin; Fibromodulin; Chondroitin Sulfate Proteoglycans; Extracellular Matrix Proteins; Endometrium; Telocytes
PubMed: 37840262
DOI: 10.1080/01913123.2023.2270660 -
Frontiers in Cell and Developmental... 2023
PubMed: 37519300
DOI: 10.3389/fcell.2023.1240481 -
Annals of Biomedical Engineering Mar 2024Interest in studying neonatal development and the improved healing response observed in neonates is increasing, with the goal of using this work to create better...
Interest in studying neonatal development and the improved healing response observed in neonates is increasing, with the goal of using this work to create better therapeutics for tendon injury. Decorin and biglycan are two small leucine-rich proteoglycans that play important roles in collagen fibrillogenesis to develop, maintain, and repair tendon structure. However, little is known about the roles of decorin and biglycan in early neonatal development and healing. The goal of this study was to determine the effects of decorin and biglycan knockdown on Achilles tendon structure and mechanics during neonatal development and recovery of these properties after injury of the neonatal tendon. We hypothesized that knockdown of decorin and biglycan would disrupt the neonatal tendon developmental process and produce tendons with impaired mechanical and structural properties. We found that knockdown of decorin and biglycan in an inducible, compound decorin/biglycan knockdown model, both during development and after injury, in neonatal mice produced tendons with reduced mechanical properties. Additionally, the collagen fibril microstructure resembled an immature tendon with a large population of small diameter fibrils and an absence of larger diameter fibrils. Overall, this study demonstrates the importance of decorin and biglycan in facilitating tendon growth and maturation during neonatal development.
Topics: Animals; Mice; Achilles Tendon; Biglycan; Collagen; Decorin; Extracellular Matrix Proteins
PubMed: 38079083
DOI: 10.1007/s10439-023-03414-8 -
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