• Title/Summary/Keyword: transforming growth factor-B

Search Result 101, Processing Time 0.025 seconds

The effects of berberine on ischemia-reperfusion injuries in an experimental model of ovarian torsion

  • Filiz Yilmaz;Orkun Ilgen;Alper Mankan;Bayram Yilmaz;Sefa Kurt
    • Clinical and Experimental Reproductive Medicine
    • /
    • v.50 no.4
    • /
    • pp.292-298
    • /
    • 2023
  • Objective: Ovarian torsion is a gynecological disorder that causes ischemia-reperfusion injuries in the ovary. Our study investigated berberine's short- and long-term effects on ovarian ischemia-reperfusion injuries. Methods: This study included 28 Wistar albino female rats weighing 180 to 220 g, which were divided into four groups: sham (S), torsion/detorsion (T/D), torsion/ detorsion+single dose berberine (T/D+Bb), and torsion/detorsion+15 days berberine (T/D+15Bb). The torsion and detorsion model was applied in all non-sham groups. In the T/D+Bb group, a single dose of berberine was administered, while in the T/D+15Bb group, berberine was administered over a period of 15 days. After the rats were euthanized, their ovaries were excised. The left ovaries were used for histopathologic evaluation, which included ovarian injury scoring and follicle count, while the right ovaries were used for biochemical analyses (tissue transforming growth factor-β [TGF-β] and alpha-smooth muscle actin [α-SMA] levels). Results: The histopathologic evaluation scores for the ovaries were significantly lower in the T/D+B group (p<0.05) and the T/D+15B group (p<0.005) than in the T/D group. The follicle counts in the T/D group were lower than those in both the sham and treated groups (p<0.005). The TGF-β levels were significantly lower in the T/D+15B group (p<0.005), whereas the α-SMA levels did not show a significant difference. Conclusion: Both short- and long-term berberine use could potentially have therapeutic effects on ovarian torsion. Long-term berberine use exhibited anti-inflammatory effects by reducing TGF-β levels, thereby preventing ischemia-reperfusion injuries. Therefore, we suggest that long-term berberine use could be beneficial for ovarian torsion.

Antioxidant Activity of Cannabidiol (CBD) and Effect on Its Proliferation in Human Dermal Papilla Cells (칸나비디올(CBD)의 항산화 활성 및 인간 모유두 세포 증식에 미치는 영향)

  • Soo Hyun Kim;Kyu-Sang Sim;Jung Yoon Cheon;Jae-Woong Jang;Su Jin Jeong;Ye Hei Seo;Hye Myoung Ahn;Bong-Geun Song;Gi-Seok Kwon;Jung-Bok Lee
    • Journal of Life Science
    • /
    • v.33 no.3
    • /
    • pp.234-241
    • /
    • 2023
  • At present, many countries around the world are legalizing cannabis and its products, and research on various treatments using cannabis is being actively conducted. However, the cannabis plant contains other compounds whose biological effects have not yet been established. We investigated the effect of cannabidiol (CBD) on hair growth in human dermal papilla cells (HDPCs). 2,2'-Azino-bis (3-ethylbenzothiazolin-6-sulfonic acid) (ABTS) and 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging assays were performed to determine the antioxidant activity of CBD. The HDPCs viability of CBD was examined via water-soluble tetrazolium salt (WST-1) assay. The expression of hair-loss-related markers in HDPCs by CBD treatment was analyzed by real-time PCR and western blotting. The DPPH, ABTS radical scavenging activity assay showed that CBD had superior antioxidant activities. In HDPCs, CBD increased cellular proliferation at concentrations without cytotoxicity. It also increased the expressions of fibroblast growth factor 1 (FGF1), fibroblast growth factor 7 (FGF7), vascular endothelial growth factor (VEGF), and insulin-like growth factor (IGF). These results correlated with a decrease in the expression of inhibition-related factors, such as androgen receptor (AR) and transforming growth factor beta 1 (TGF-B1). Moreover, CBD resulted in a significant increase in the phosphorylation of AKT and extracellular signal-regulated kinase (ERK). Therefore, it is suggested that CBD may be a potential remedy for the treatment of alopecia.

Development of Ginseng yogurt fermented by Bifidobacterium spp (Bifidobacterium을 이용한 인삼 요구르트의 개발)

  • Kim, Na-Young;Han, Myung-Joo
    • Korean journal of food and cookery science
    • /
    • v.21 no.5
    • /
    • pp.575-584
    • /
    • 2005
  • The objective of this study was to develop bioactive ginseng yogurt, fermented by B. minimum KK-1 and B. cholerium KK-2, which showed transforming activity of ginseng extract to compound K. Among older people, 3% ginseng yogurt fermented by B. minimum KK-1 and mixed with Bifidobacterium KK-1, KK-2 showed the highest overall acceptability(6.80, 6.80) among 1%(3.87, 3.67), 2%(4.40, 4.53) and 3% ginseng yogurt. The pH of ginseng yogurt was lower than that of plain yogurt. During 9 days of storage, the pH of each yogurt slightly decreased and then increased until 15 days of storage. The 3 8.25 log CFU/g and B. cholerium KK-2; 7.78 log CFU/g). Therefore, ginseng might be used as a growth factor during the fermentation of yogurt. The L value of ginseng yogurt decreased, and the a and b values increased, with increasing ginseng concentration.

Inhibitors of DNA methylation support TGF-β1-induced IL11 expression in gingival fibroblasts

  • Sufaru, Irina-Georgeta;Beikircher, Gabriel;Weinhaeusel, Andreas;Gruber, Reinhard
    • Journal of Periodontal and Implant Science
    • /
    • v.47 no.2
    • /
    • pp.66-76
    • /
    • 2017
  • Purpose: Oral wound healing requires gingival fibroblasts to respond to local growth factors. Epigenetic silencing through DNA methylation can potentially decrease the responsiveness of gingival fibroblasts to local growth factors. In this study, our aim was to determine whether the inhibition of DNA methylation sensitized gingival fibroblasts to transforming growth factor-${\beta}1$ (TGF-${\beta}1$). Methods: Gingival fibroblasts were exposed to 5-aza-2'-deoxycytidine (5-aza), a clinically approved demethylating agent, before stimulation with TGF-${\beta}1$. Gene expression changes were evaluated using quantitative polymerase chain reaction (PCR) analysis. DNA methylation was detected by methylation-sensitive restriction enzymes and PCR amplification. Results: We found that 5-aza enhanced TGF-${\beta}1$-induced interleukin-11 (IL11) expression in gingival fibroblasts 2.37-fold (P=0.008). 5-aza had no significant effects on the expression of proteoglycan 4 (PRG4) and NADPH oxidase 4 (NOX4). Consistent with this, 5-aza caused demethylation of the IL11 gene commonly next to a guanosine (CpG) island in gingival fibroblasts. The TGF-${\beta}$ type I receptor kinase inhibitor SB431542 impeded the changes in IL11 expression, indicating that the effects of 5-aza require TGF-${\beta}$ signaling. 5-aza moderately increased the expression of TGF-${\beta}$ type II receptor (1.40-fold; P=0.009), possibly enhancing the responsiveness of fibroblasts to TGF-${\beta}1$. As part of the feedback response, 5-aza increased the expression of the DNA methyltransferases 1 (DNMT1) (P=0.005) and DNMT3B (P=0.002), which are enzymes responsible for gene methylation. Conclusions: These in vitro data suggest that the inhibition of DNA methylation by 5-aza supports TGF-${\beta}$-induced IL11 expression in gingival fibroblasts.

Peroxisome Proliferator-Activated Receptor Gamma Agonist Attenuates Liver Fibrosis by Several Fibrogenic Pathways in an Animal Model of Cholestatic Fibrosis

  • Alatas, Fatima Safira;Matsuura, Toshiharu;Pudjiadi, Antonius Hocky;Wijaya, Stephanie;Taguchi, Tomoaki
    • Pediatric Gastroenterology, Hepatology & Nutrition
    • /
    • v.23 no.4
    • /
    • pp.346-355
    • /
    • 2020
  • Purpose: Peroxisome proliferator-activated receptor gamma (PPAR-γ) has a key role in hepatic fibrogenesis by virtue of its effect on the hepatic stellate cells (HSCs). Although many studies have shown that PPAR-γ agonists inhibit liver fibrosis, the mechanism remains largely unclear, especially regarding the cross-talk between PPAR-γ and other potent fibrogenic factors. Methods: This experimental study involved 25 male Wistar rats. Twenty rats were subjected to bile duct ligation (BDL) to induce liver fibrosis, further divided into an untreated group (BDL; n=10) and a group treated with the PPAR-γ agonist thiazolidinedione (TZD), at 14 days post-operation (BDL+TZD; n=10). The remaining 5 rats had a sham operation (sham; n=5). The effect of PPAR-γ agonist on liver fibrosis was evaluated by histopathology, protein immunohistochemistry, and mRNA expression quantitative polymerase chain reaction. Results: Histology and immunostaining showed markedly reduced collagen deposition, bile duct proliferation, and HSCs in the BDL+TZD group compared to those in the BDL group (p<0.001). Similarly, significantly lower mRNA expression of collagen α-1(I), matrix metalloproteinase-2, platelet-derived growth factor (PDGF)-B chain, and connective tissue growth factor (CTGF) were evident in the BDL+TZD group compared to those in the BDL group (p=0.0002, p<0.035, p<0.0001, and p=0.0123 respectively). Moreover, expression of the transforming growth factor beta1 (TGF-β1) was also downregulated in the BDL+TZD group (p=0.0087). Conclusion: The PPAR-γ agonist inhibits HSC activation in vivo and attenuates liver fibrosis through several fibrogenic pathways. Potent fibrogenic factors such as PDGF, CTGF, and TGF-β1 were downregulated by the PPAR-γ agonist. Targeting PPAR-γ activity may be a potential strategy to control liver fibrosis.

PRODUCTION OF TRANSFORMING GROWTH FACTOR-${\beta}_1$ IN HUMAN FIBROBLASTS INDUCED WITH BACTERIAL TOXINS (세균 독소를 작용시킨 섬유아 세포에서 Transforming Growth Factor-${\beta}_1$의 생성)

  • Lee, Seong-Geun;Kim, Kwang-Hyuk
    • Journal of the Korean Association of Oral and Maxillofacial Surgeons
    • /
    • v.26 no.4
    • /
    • pp.345-354
    • /
    • 2000
  • TGF-${\beta}_1$ is a potent chemotactic factor for inflammatory cells and fibroblasts. It also stimulates the celluar source and components of extracellular matrix and the production of proteinase inhibitors. Collectively, these biologic activities lead to the accumulation and stabilization of the nascent matrix, which is vital to wound healing. The objective of this study is to investigate production of TGF-${\beta}_1$ in vitro fibroblast culture in the presence of Staphylococcus enterotoxin B(SEB) and/or lipopolysaccharide(LPS) and to elucidate the role of TGF-${\beta}_1$ which may be responsible for wound healing. The fibroblasts were originated from facial dermis and hypertrophic scar in 26 year-old male patient. In the presence of LPS($0.01{\mu}g$, $0.1{\mu}g$, $1.0{\mu}g$), SEB($0.01{\mu}g$, $0.1{\mu}g$, $1.0{\mu}g$) respectively, cells($5{\times}10^3ml$) were cultivated in vitro. At 1, 3, and 5 days after incubation, cells were counted. Also, cells($2.5{\times}10^5ml$) were cultivated in EMEM with LPS(0.01, 0.1 and $1.0{\mu}g$), SEB(0.01, 0.1 and $1.0{\mu}g$) respectively and LPS($0.1{\mu}g$) and SEB($0.1{\mu}g$) in combination for 24, 48, and 72 hours respectively. Culture supernatants were harvested at 1, 2, and 3 days after incubation period and triplicate culture supernatants were pooled and TGF-${\beta}_1$ was assayed in duplicate. The results were as follows. 1. In facial dermal fibroblast induced with SEB and LPS respectively or in combination, the suppression of cell proliferation occurred very significantly at 1 day after incubation, compared with the control. In SEB exposure, the production of TGF-${\beta}_1$ was decreased very significantly at 1 day after incubation, compared with the control. However, in LPS, SEB and LPS exposure, the production of TGF-${\beta}_1$ was increased very significantly at 1 day after incubation, compared with the control. 2. In hypertrophic scar fibroblast induced with SEB and LPS respectively or in combination, the suppression of cell proliferation did not occur at 1 day after incubation, compared with the control. In SEB and LPS exposure in combination, the production of TGF-${\beta}_1$ was increased very significantly at 1 day after incubation, compared with the control. However, the production of TGF-${\beta}_1$ did not occur in SEB and LPS exposure respectively. In conclusion, the concentration of bacterial toxins and the incubation period correlated with cell proliferation and production of TGF-${\beta}_1$ very significantly and both fibroblasts have different phenotype each other in this regard. This data suggest that the significant production of TGF-${\beta}_1$ may develope abnormal wound healing associated with tissue fibroproliferative disorder, such as hypertrophic scar and keloid formation.

  • PDF

Clinical Predictive Value of Serum Angiogenic Factor in Patients with Osteosarcoma

  • Chen, Zhe;Chen, Qi-Xin;Hou, Zhao-Yang;Hu, Jiong;Cao, Yan-Guang
    • Asian Pacific Journal of Cancer Prevention
    • /
    • v.13 no.9
    • /
    • pp.4823-4826
    • /
    • 2012
  • Objective: To explore serum angiogenic factor expression in patients with osteosarcoma and its relationship with metastasis. Methods: Immunohistochemistry was used to test the expression of CD34 and FVIII-Rag in osteosarcoma tissues of 36 patients (osteosarcoma group) and microvessel density (MVD) was also recorded. In addition, ELISA was used to test the level of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), transforming growth factor-${\beta}1$ (TGF-${\beta}1$) and endostatin (ES) in the osteosarcoma group and in a control group. Results: VEGF and ES level were significantly higher than in the control group before operation (P<0.01), VEGF, bFGF and TGF-${\beta}1$ correlating with the ES level (P<0.01). Serum VEGF and ES levels of osteosarcoma patients before surgery were closely related to relapse and metastasis; moreover, serum VEGF increased with MVD (P<0.01). Postoperative VEGF and ES levels were lower than the preoperation values (P<0.01); ES level in relapse group was significantly higher than that of the non-relapse group (P<0.01). Conclusion: Preoperative serum VEGF and postoperative ES levels have great predictive value with regard to relapse of osteosarcoma patients.

4-Hexylresorcinol induced angiogenesis potential in human endothelial cells

  • Kim, Min-Keun;Kim, Seong-Gon;Lee, Suk Keun
    • Maxillofacial Plastic and Reconstructive Surgery
    • /
    • v.42
    • /
    • pp.23.1-23.11
    • /
    • 2020
  • Background: 4-Hexylresorcinol (4HR) is able to increase angiogenesis. However, its molecular mechanism in the human endothelial cells has not been clarified. Methods: As endothelial cells are important in angiogenesis, we treated the human umbilical vein endothelial cells (HUVECs) with 4HR and investigated protein expressional changes by immunoprecipitation high-performance liquid chromatography (IP-HPLC) using 96 antisera. Results: Here, we found that 4HR upregulated transforming growth factor-β (TGF-β)/SMAD/vascular endothelial growth factor (VEGF) signaling, RAF-B/ERK and p38 signaling, and M2 macrophage polarization pathways. 4HR also increased expression of caspases and subsequent cellular apoptosis. Mechanistically, 4HR increased TGF-β1 production and subsequent activation of SMADs/VEGFs, RAF-B/ERK and p38 signaling, and M2 macrophage polarization. Conclusion: Collectively, 4HR activates TGF-β/SMAD/VEGF signaling in endothelial cells and induced vascular regeneration and remodeling for wound healing.