scholarly journals Osteogenic Response to Polysaccharide Nanogel Sheets of Human Fibroblasts After Conversion Into Functional Osteoblasts by Direct Phenotypic Cell Reprogramming

2021 ◽  
Vol 9 ◽  
Author(s):  
Kei Nakai ◽  
Kenta Yamamoto ◽  
Tsunao Kishida ◽  
Shin-ichiro Kotani ◽  
Yoshiki Sato ◽  
...  
Keyword(s):  
Transforming Growth Factor ◽  
Human Fibroblasts ◽  
Control Cell ◽  
Transforming Growth Factor Β ◽  
Dermal Fibroblasts ◽  
Control Group ◽  
Raman Spectroscopic ◽  
Freeze Dried ◽  
Osteogenic Response ◽  
Significant Difference

Human dermal fibroblasts (HDFs) were converted into osteoblasts using a ALK inhibitor II (inhibitor of transforming growth factor-β signal) on freeze-dried nanogel-cross-linked porous (FD-NanoClip) polysaccharide sheets or fibers. Then, the ability of these directly converted osteoblasts (dOBs) to produce calcified substrates and the expression of osteoblast genes were analyzed in comparison with osteoblasts converted by exactly the same procedure but seeded onto a conventional atelocollagen scaffold. dOBs exposed to FD-NanoClip in both sheet and fiber morphologies produced a significantly higher concentration of calcium deposits as compared to a control cell sample (i.e., unconverted fibroblasts), while there was no statistically significant difference in calcification level between dOBs exposed to atelocollagen sheets and the control group. The observed differences in osteogenic behaviors were interpreted according to Raman spectroscopic analyses comparing different polysaccharide scaffolds and Fourier transform infrared spectroscopy analyses of dOB cultures. This study substantiates a possible new path to repair large bone defects through a simplified transplantation procedure using FD-NanoClip sheets with better osteogenic outputs as compared to the existing atelocollagen scaffolding material.

Acyltransferase skinny hedgehog regulates TGFβ-dependent fibroblast activation in SSc

2019 ◽  
Vol 78 (9) ◽  
pp. 1269-1273 ◽  
Author(s):  
Ruifang Liang ◽  
Rosebeth Kagwiria ◽  
Ariella Zehender ◽  
Clara Dees ◽  
Christina Bergmann ◽  
...  
Keyword(s):  
Long Range ◽  
Transforming Growth Factor ◽  
Human Fibroblasts ◽  
Transforming Growth Factor Β ◽  
Dermal Fibroblasts ◽  
Myofibroblast Differentiation ◽  
Dependent Manner ◽  
Hedgehog Signalling ◽  
Fibroblast Activation ◽  
Novel Approach

ObjectivesSystemic sclerosis (SSc) is characterised by aberrant hedgehog signalling in fibrotic tissues. The hedgehog acyltransferase (HHAT) skinny hedgehog catalyses the attachment of palmitate onto sonic hedgehog (SHH). Palmitoylation of SHH is required for multimerisation of SHH proteins, which is thought to promote long-range, endocrine hedgehog signalling. The aim of this study was to evaluate the role of HHAT in the pathogenesis of SSc.MethodsExpression of HHAT was analysed by real-time polymerase chain reaction(RT-PCR), immunofluorescence and histomorphometry. The effects of HHAT knockdown were analysed by reporter assays, target gene studies and quantification of collagen release and myofibroblast differentiation in cultured human fibroblasts and in two mouse models.ResultsThe expression of HHAT was upregulated in dermal fibroblasts of patients with SSc in a transforming growth factor-β (TGFβ)/SMAD-dependent manner. Knockdown of HHAT reduced TGFβ-induced hedgehog signalling as well as myofibroblast differentiation and collagen release in human dermal fibroblasts. Knockdown of HHAT in the skin of mice ameliorated bleomycin-induced and topoisomerase-induced skin fibrosis.ConclusionHHAT is regulated in SSc in a TGFβ-dependent manner and in turn stimulates TGFβ-induced long-range hedgehog signalling to promote fibroblast activation and tissue fibrosis. Targeting of HHAT might be a novel approach to more selectively interfere with the profibrotic effects of long-range hedgehog signalling.

scholarly journals The Abnormal Expression of HSP70 Is Related to Treg / Th17 Imbalance in PCOS Patients

2021 ◽  
Author(s):  
Yiqing Yang ◽  
Jing Xia ◽  
Zhe Yang ◽  
Gengxiang Wu ◽  
Jing Yang
Keyword(s):  
Transforming Growth Factor ◽  
Polycystic Ovary ◽  
Rank Correlation ◽  
Transforming Growth Factor Β ◽  
Control Group ◽  
Low Grade ◽  
Strong Negative Correlation ◽  
Abnormal Expression ◽  
Significant Difference ◽  
Pcos Group

Abstract Background: Polycystic ovary syndrome (PCOS) is a disease with chronic nonspecific low-grade inflammation. The imbalance of immune cells exists in PCOS. Several studies have found that heat shock protein 70 (HSP70) may be involved in the immunological pathogenesis of PCOS, but the relationship between HSP70 and Regulatory T cell (Treg)/ T helper cell 17(Th17) ratio remains unclear. This study aims to explore the correlation between HSP70 and Treg/Th17 ratio, and to find out the role of HSP70 in the immunological etiology of PCOS.Results: There was no significant difference in age and body mass index (BMI) between two groups. The concentrations of basal estradiol (E2), basal follicle stimulating hormone (FSH) didn’t show significant difference between two groups. The concentrations of basal luteinizing hormone (LH) (P < 0.05), testosterone (T) (P < 0.01), glucose (P < 0.001) and insulin (P < 0.001) in PCOS patients were significantly higher than those in control group. The expressions of HSP70 were significantly higher in serum in the PCOS group (P < 0.001). The percentage of Treg cells was significantly lower (P < 0.05), while the percentage of the Th17 cells of the PCOS group was significantly higher than that of the control group (P < 0.05). The ratio of Treg/Th17 in PCOS group was significantly lower (P < 0.001). The concentrations of Interleukin (IL)-6, IL-17 and IL-23 were significantly higher, while the levels of IL-10 and Transforming growth factor-β (TGF-β) were significantly lower in PCOS group (P < 0.001). Spearman rank correlation analysis showed strong negative correlation of serum HSP70 levels with Treg/Th17 ratio, IL-10 and TGF-β levels. In contrast, HSP70 levels were significantly positively correlated with IL-6, IL-17, IL-23, LH, T, insulin, and glucose levels.Conclusion: The abnormal expression of HSP70 is correlated with Treg/Th17 imbalance and corresponding cytokines, which indicates that HSP70 may play an important role in PCOS immunologic pathogenesis.

scholarly journals The abnormal level of HSP70 is related to Treg/Th17 imbalance in PCOS patients

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Yiqing Yang ◽  
Jing Xia ◽  
Zhe Yang ◽  
Gengxiang Wu ◽  
Jing Yang
Keyword(s):  
Transforming Growth Factor ◽  
Polycystic Ovary ◽  
Rank Correlation ◽  
Transforming Growth Factor Β ◽  
Control Group ◽  
Low Grade ◽  
Strong Negative Correlation ◽  
Significant Difference ◽  
Pcos Group ◽  
Abnormal Level

Abstract Background Polycystic ovary syndrome (PCOS) is a disease with chronic nonspecific low-grade inflammation. The imbalance of immune cells exists in PCOS. Several studies have found that heat shock protein 70 (HSP70) may be involved in the immunological pathogenesis of PCOS, but the relationship between HSP70 and Regulatory T cell (Treg)/T helper cell 17(Th17) ratio remains unclear. This study aims to explore the correlation between HSP70 and Treg/Th17 ratio and to provide evidence for the role of HSP70 in the immunological etiology of PCOS. Results There was no significant difference in age and body mass index (BMI) between the two groups. The concentrations of basal estradiol (E2), basal follicle-stimulating hormone (FSH) did not show a significant difference between the two groups. The concentrations of basal luteinizing hormone (LH) (P < 0.01), testosterone (T) (P < 0.01), glucose (P < 0.001) and insulin (P < 0.001) in PCOS patients were significantly higher than those in the control group. The protein levels of HSP70 were significantly higher in serum in the PCOS group (P < 0.001). The percentage of Treg cells was significantly lower (P < 0.01), while the percentage of the Th17 cells of the PCOS group was significantly higher than that of the control group (P < 0.05). The ratio of Treg/Th17 in the PCOS group was significantly lower (P < 0.001). The concentrations of Interleukin (IL)-6, IL-17, and IL-23 were significantly higher, while the levels of IL-10 and Transforming growth factor-β (TGF-β) were significantly lower in the PCOS group (P < 0.001). Spearman rank correlation analysis showed a strong negative correlation of serum HSP70 levels with Treg/Th17 ratio, IL-10, and TGF-β levels. In contrast, HSP70 levels were significantly positively correlated with IL-6, IL-17, IL-23, LH, insulin, and glucose levels. Conclusion The abnormal level of HSP70 is correlated with Treg/Th17 imbalance and corresponding cytokines, which indicates that HSP70 may play an important role in PCOS immunologic pathogenesis.

Expression of CD4+CD25+Foxp3+ Regulatory T Cells, Interleukin 10 and Transforming Growth Factor β in Newly Diagnosed Type 2 Diabetic Patients

2017 ◽  
Vol 126 (02) ◽  
pp. 96-101 ◽  
Author(s):  
Ning Yuan ◽  
Hai-feng Zhang ◽  
Qi Wei ◽  
Ping Wang ◽  
Wei-ying Guo
Keyword(s):  
Insulin Resistance ◽  
T Cells ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Interleukin 10 ◽  
Obese Group ◽  
Control Group ◽  
Newly Diagnosed ◽  
Significant Difference

Abstract Background Recent studies have shown that dysfunction and decrease of regulatory T cells (Tregs) correlates with insulin resistance (IR), one of the most significant mechanisms for type 2 diabetes mellitus (T2DM). To examine potential relationships among Tregs, IR, blood lipid content, and related cytokines, we investigated the frequency of CD4+CD25+Foxp3+ Tregs, as well as expression levels of interleukin 10 (IL-10) and transforming growth factor-β (TGF-β) in newly diagnosed T2DM patients. Methods Fifty-one newly diagnosed T2DM patients and 55 control individuals were enrolled. According to body mass index (BMI), the T2DM patients were grouped into non-obese and obese groups. Blood was collected in ethylene diamine tetraacetic acid (EDTA) anticoagulant tubes for detection of CD4+CD25+Foxp3+ Tregs by flow cytometry. Serum was collected to quantify IL-10 and TGF-β levels by enzyme-linked immunosorbent assay (ELISA). By comparing percentages of Tregs between non-obese and obese groups, correlation with Treg frequency, homeostasis model assessment of insulin resistance (HOMA-IR), IL-10 and TGF-β was examined. Results The percentage of CD4+CD25+Foxp3+ Tregs in the newly diagnosed T2DM group was significantly lower than in the control group (P<0.01). Further, levels of IL-10 and TGF-β were also lower in the T2DM group (P<0.05). The level of IL-10 was remarkably lower in the obese group than in the non-obese and the control groups (P<0.01), but there was no significant difference between non-obese group and the control group. The level of TGF-β was lower in obese group than in the control group (P<0.05). There was no significant difference between non-obese group and the control group. The frequency of CD4+CD25+Foxp3+ Tregs in the obese group was significantly lower than in the non-obese group (P<0.05). In the obese group, the percentage of Tregs negatively correlated with HOMA-IR and positively correlated with TGF-β (P<0.05). There was no obvious correlation between Treg and HOMA-IR in the non-obese group. Conclusion The percentage of CD4+CD25+Foxp3+ Tregs and levels of related cytokines IL-10 and TGF-β were precipitously decreased in newly diagnosed T2DM patients. Therefore, the function of Tregs in limiting the proinflammatory milieu represents an important pathogenic mediator of the development of obesity-induced IR in newly diagnosed T2DM patients. Notably, TGF-β may play an important role in this process. Thus, enhancing expression of Tregs may improve IR in newly diagnosed T2DM patients with obesity.

scholarly journals Dopamine adjusts the circadian gene expression of Per2 and Per3 in human dermal fibroblasts from ADHD patients

2021 ◽  
Author(s):  
Frank Faltraco ◽  
Denise Palm ◽  
Adriana Uzoni ◽  
Lena Borchert ◽  
Frederick Simon ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dermal Fibroblast ◽  
Sleep Onset ◽  
Dermal Fibroblasts ◽  
Control Group ◽  
Adhd Group ◽  
Healthy Controls ◽  
Circadian Gene ◽  
Significant Difference ◽  
Circadian Preference

AbstractA link between dopamine levels, circadian gene expression, and attention deficit hyperactivity disorder (ADHD) has already been demonstrated. The aim of this study was to investigate the extent of these relationships by measuring circadian gene expression in primary human-derived dermal fibroblast cultures (HDF) after dopamine exposure. We analyzed circadian preference, behavioral circadian and sleep parameters as well as the circadian gene expression in a cohort of healthy controls and participants with ADHD. Circadian preference was evaluated with German Morningness-Eveningness-Questionnaire (D-MEQ) and rhythms of sleep/wake behavior were assessed via actigraphy. After ex vivo exposure to different dopamine concentrations in human dermal fibroblast (HDF) cultures, the rhythmicity of circadian gene expression (Clock, Bmal1, Per1-3, Cry1) was analyzed via qRT-PCR. We found no statistical significant effect in the actigraphy of both groups (healthy controls, ADHD group) for mid-sleep on weekend days, mid-sleep on weekdays, social jetlag, wake after sleep onset, and total number of wake bouts. D-MEQ scores indicated that healthy controls had no evening preference, whereas subjects with ADHD displayed both definitive and moderate evening preferences. Dopamine has no effect on Per3 expression in healthy controls, but produces a significant difference in the ADHD group at ZT24 and ZT28. In the ADHD group, incubation with dopamine, either 1 µM or 10 µM, resulted in an adjustment of Per3 expression to control levels. A similar effect also was found in the expression of Per2. Statistical significant differences in the expression of Per2 (ZT4) in the control group compared to the ADHD group were found, following incubation with dopamine. The present study illustrates that dopamine impacts on circadian function. The results lead to the suggestion that dopamine may improve the sleep quality as well as ADHD symptoms by adjustment of the circadian gene expression, especially for Per2 and Per3.

scholarly journals The Effects of Rice Husk Liquid Smoke in Porphyromonas gingivalis-Induced Periodontitis

2021 ◽  
Author(s):  
Theresia Indah Budhy ◽  
Ira Arundina ◽  
Meircurius Dwi Condro Surboyo ◽  
Anisa Nur Halimah
Keyword(s):  
Growth Factor ◽  
Porphyromonas Gingivalis ◽  
Rice Husk ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Control Group ◽  
Proliferation Markers ◽  
Liquid Smoke ◽  
Tnf Α ◽  
Factor Α

Abstract Objectives The purpose of this study is to analyze the effects of rice husk liquid smoke in Porphyromonas gingivalis-induced periodontitis in the inflammatory and proliferation marker such as nuclear factor kappa β (NF-kB), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), transforming growth factor-β (TGF-β), fibroblast growth factor 2 (FGF2), collagen type 1 (COL-1) expression, and the number of macrophages, lymphocytes, and fibroblasts. Materials and Methods Rice husk liquid smoke is obtained by the pyrolysis process. Porphyromonas gingivalis-induced periodontitis in 20 μL phosphate-buffered saline containing 1 × 109 CFU was injected into the lower anterior gingival sulcus of Wistar rats. The periodontitis was then treated with 20 μL/20 g body weight of rice husk liquid smoke once a day for 2 and 7 days, respectively. After treatment, the bone and lower anterior gingival sulcus were analyzed with immunohistochemistry and hematoxylin–eosin staining. Results The treatment of periodontitis with rice husk liquid smoke showed a lower NF-kB, TNF-α, and IL-6 expression and a higher TGF-β, FGF2, and COL-1 expression than the control after treatment for 2 and 7 days (p < 0.05), respectively. The number of macrophages and fibroblasts was also higher when compared with the control group (p < 0.05), but the number of lymphocytes was lower than the control (p < 0.05). Conclusion Rice husk liquid smoke showed its effects on Porphyromonas gingivalis-induced periodontitis with a decrease in inflammatory markers and an increase in proliferation markers. The development of a rice husk liquid smoke periodontitis treatment is promising.

scholarly journals Stimulation of the chemotactic migration of human fibroblasts by transforming growth factor beta.

1987 ◽  
Vol 165 (1) ◽  
pp. 251-256 ◽  
Author(s):  
A E Postlethwaite ◽  
J Keski-Oja ◽  
H L Moses ◽  
A H Kang
Keyword(s):  
Growth Factor ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Human Fibroblasts ◽  
Critical Role ◽  
Dermal Fibroblasts ◽  
Type I ◽  
Tgf Beta ◽  
Chemotactic Migration ◽  
Growth Factor Beta

Transforming growth factor beta (TGF-beta) is a potent chemoattractant in vitro for human dermal fibroblasts. Intact disulfide and perhaps the dimeric structure of TGF-beta is essential for its ability to stimulate chemotactic migration of fibroblasts, since reduction with 2-ME results in a marked loss of its potency as a chemoattractant. Although epidermal growth factor (EGF) appears to be capable of modulating some effects of TGF-beta, it does not alter the chemotactic response of fibroblasts to TGF-beta. Specific polyvalent rabbit antibodies to homogeneously pure TGF-beta block its chemotactic activity but has no effect on the other chemoattractants tested (platelet-derived growth factor, fibronectin, and denatured type I collagen). Since TGF-beta is secreted by a variety of neoplastic and normal cells including platelets, monocytes/macrophages, and lymphocytes, it may play a critical role in vivo in embryogenesis, host response to tumors, and the repair response that follows damage to tissues by immune and nonimmune reactions.

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