• Title/Summary/Keyword: Transforming Growth Factor Beta1

Search Result 375, Processing Time 0.023 seconds

Vinpocetine, a phosphodiesterase 1 inhibitor, mitigates atopic dermatitis-like skin inflammation

  • Yeon Jin Lee;Jin Yong Song;Su Hyun Lee;Yubin Lee;Kyu Teak Hwang;Ji-Yun Lee
    • The Korean Journal of Physiology and Pharmacology
    • /
    • v.28 no.4
    • /
    • pp.303-312
    • /
    • 2024
  • Atopic dermatitis (AD) is the most common inflammatory pruritic skin disease worldwide, characterized by the infiltration of multiple pathogenic T lymphocytes and histological symptoms such as epidermal and dermal thickening. This study aims to investigate the effect of vinpocetine (Vinp; a phosphodiesterase 1 inhibitor) on a 1-chloro-2,4-dinitrobenzene (DNCB)-induced AD-like model. DNCB (1%) was administered on day 1 in the AD model. Subsequently, from day 14 onward, mice in each group (Vinp-treated groups: 1 mg/kg and 2 mg/kg and dexamethasone-treated group: 2 mg/kg) were administered 100 µl of a specific drug daily, whereas 0.2% DNCB was administered every other day for 30 min over 14 days. The Vinp-treated groups showed improved Eczema Area and Severity Index scores and trans-epidermal water loss, indicating the efficacy of Vinp in improving AD and enhancing skin barrier function. Histological analysis further confirmed the reduction in hyperplasia of the epidermis and the infiltration of inflammatory cells, including macrophages, eosinophils, and mast cells, with Vinp treatment. Moreover, Vinp reduced serum concentrations of IgE, interleukin (IL)-6, IL-13, and monocyte chemotactic protein-1. The mRNA levels of IL-1β, IL-6, Thymic stromal lymphopoietin, and transforming growth factor-beta (TGF-β) were reduced by Vinp treatment. Reduction of TGF-β protein by Vinp in skin tissue was also observed. Collectively, our results underscore the effectiveness of Vinp in mitigating DNCB-induced AD by modulating the expression of various biomarkers. Consequently, Vinp is a promising therapeutic candidate for treating AD.

Effect of Soy Isoflavones on the Expression of $TGF-{\beta}1$ and Its Receptors in Cultured Human Breast Cancer Cell Lines

  • Kim Young-Hwa;Jin Kyong-Suk;Lee Yong-Woo
    • Biomedical Science Letters
    • /
    • v.11 no.2
    • /
    • pp.175-183
    • /
    • 2005
  • The two major isoflavones in soy, genistein and daidzein, are well known to prevent hormone-dependent cancers by their anti estrogenic activity. The exact molecular mechanisms for the protective action are, however, not provided yet. It has been reported that genistein and daidzein have a potential anticancer activity through their antiproliferative effect in many hormone-dependent cancer cell lines. Transforming growth $factor-\beta1(TGF-\beta1)$ has also been found to have cell growth inhibitory effect, especially in mammary epithelial cells. This knowledge led to a hypothetical mechanism that the soy isoflavones-induced growth inhibitory effect can be derived from the regulation of $TGF-\beta1$ and $TGF-\beta$ receptors. In order to test this hypothesis, the effects of the soy isoflavones at various concentrations and periods on the expression of $TGF-\beta1$and $TGF-\beta$ receptors were investigated by using Northern blot analysis in human breast carcinoma epithelial cell lines, an estrogen receptor positive cell line (MCF-7) and an estrogen receptor negative cell line (MDA-MB-231). As a result, only genistein has shown a profound dose-dependent effect on $TGF-\beta1$ expression in the $ER^+$ cell line within the range of doses tested, and the expression levels are correspondent to their inhibitory activities of cell growth. Moreover, daidzein showed down-regulated $TGF-\beta1$ expression at a low dose, the cell growth proliferation was promoted at the same condition. Therefore, antiproliferative activity of the soy isoflavones can be mediated by $TGF-\beta1$ expression, and the effects are mainly, if not all, occurred by ER dependent pathway. The expression of $TGF-\beta$ receptors was induced at a lower dose than the one for $TGF-{\beta}1$ induction regardless of the presence of ER, and the expression patterns are similar to those of the cell growth inhibition. These results indicated that the regulation of $TGF-\beta$ receptor expression as well, prior to $TGF-\beta1$ expression, may be involved in the antiproliferative activity of soy isoflavones. Little or no expression of $TGF-\beta$ receptors was found in the MCF-7 and MDA-MB-231 cells, suggesting refractory properties of the cells to growth inhibitory effect of the $TGF-\beta$. The soy isoflavones can seemingly restore the sensitivity of growth inhibitory responses to $TGF-\beta1$ by re-inducing $TGF-\beta$ receptors expression. In conclusions, our findings presented in this study show that the antitumorigenic activity of the soy isoflavones could be mediated by not only $TGF-\beta1$induction but $TGF-\beta$ receptor restoration. Thus, soy isoflavones could be good model molecules to develop new nonsteroidal antiestrogenic chemopreventive agents, associated with, regulation of $TGF-\beta$ and its receptors.

  • PDF

The influence of sodium hypochlorite concentration on the fibrin structure of human blood clots and transforming growth factor-beta 1 release: an ex vivo study

  • Anisha Mishra ;Velmurugan Natanasabapathy;Nandini Suresh
    • Restorative Dentistry and Endodontics
    • /
    • v.47 no.4
    • /
    • pp.42.1-42.11
    • /
    • 2022
  • Objective: This study investigated the effects of various concentrations of sodium hypochlorite (NaOCl) on human whole-blood clotting kinetics, the structure of the blood clots formed, and transforming growth factor (TGF)-β1 release. Materials and Methods: Human whole blood was collected from 5 healthy volunteers and divided into 4 groups: CG (control, 0.5 mL of blood), BN0.5 (0.5 mL of blood with 0.5 mL of 0.5% NaOCl), BN3 (0.5 mL of blood with 0.5 mL of 3% NaOCl), and BN5.25 (0.5 mL of blood with 0.5 mL of 5.25% NaOCl). The effects of NaOCl on clotting kinetics, structure of fibrin and cells, and release of TGF-β1 were assessed using thromboelastography (TEG), scanning electron microscopy (SEM), and enzyme-linked immunosobent assay, respectively. Statistical analysis was conducted using the Kruskal Wallis and Mann-Whitney U tests, followed by the post hoc Dunn test. A p value < 0.05 indicated statistical significance. Results: The blood samples in BN0.5 and BN3 did not clot, whereas the TEG of BN5.25 showed altered clot formation. Samples from the CG and BN3 groups could only be processed with SEM, which showed that the latter lacked fibrin formation and branching of fibers, as well as clumping of red blood cells with surface roughening and distortion. TGF-β1 release was significantly highest in BN3 when all groups were compared to CG (p < 0.05). Conclusions: Each concentration of NaOCl affected the release of TGF-β1 from blood clots and altered the clotting mechanism of blood by affecting clotting kinetics and cell structure.

Patterns of proliferation and fibrosis in a rat model of endometriosis following administration of Allium cepa

  • Hakan Kula;Orkun Ilgen;Sefa Kurt;Filiz Yilmaz
    • Clinical and Experimental Reproductive Medicine
    • /
    • v.51 no.2
    • /
    • pp.112-119
    • /
    • 2024
  • Objective: Endometriosis is a common gynecological disease among reproductive-age women. Numerous hypotheses exist regarding the pathogenesis of endometriosis. In Turkey, the consumption of Allium cepa (commonly known as the "onion cure") is a popular treatment employed to alleviate a variety of gynecological disorders. Methods: In this study, our objective was to assess the therapeutic mechanisms of the onion bulb A. cepa using an autologous endometriosis model in Sprague-Dawley rats. Previous research has shown that A. cepa possesses anti-inflammatory, antioxidant, and antiapoptotic properties. We evaluated the pathological condition of endometriotic implants by employing hematoxylin-eosin staining and Ki67 immunohistochemistry analysis. Transforming growth factor-beta 1 (TGF-β1) and alpha-smooth muscle actin (α-SMA) have been identified as profibrotic markers that are highly overexpressed in endometriotic tissues relative to eutopic endometrial tissue. Furthermore, TGF-β1 influences the differentiation and progression of endometriosis. To quantify profibrotic activity, we measured TGF-β1 and α-SMA using the immunosorbent assay method. Results: Lower histologic evaluation scores for endometriotic implants were observed in the group receiving high-dose A. cepa relative to the other groups. Ki67 expression was reduced following the high-dose A. cepa regimen, which consisted of 30% A. cepa and 70% normal feed. However, no statistically significant differences in TGF-β1 or α-SMA levels were observed among the groups (p=0.7 and p=0.778, respectively). Conclusion: The findings suggest that A. cepa could serve as a therapeutic agent in endometriosis treatment, as evidenced by the reduction in proliferative potential. Nevertheless, A. cepa was not associated with significantly lower levels of endometriosis-associated TGF-β1 or α-SMA.

Ethanol extract of medicinal herbal mixture accelerates hair growth and melanogenesis in vivo and in vitro (한약재 복합추출물이 모발 성장 및 멜라닌 생성 촉진에 미치는 영향)

  • Kim, Ji Yoon;Kim, Yoo-Jin;Kim, Moon Ju;Kim, Mi Ryeo
    • The Korea Journal of Herbology
    • /
    • v.33 no.5
    • /
    • pp.9-18
    • /
    • 2018
  • Objectives : This study was performed to determine the transdermal effects of ethanol extract from medicinal herbal mixture (SHJ) on hair growth in C57BL/6 mice and melanogenesis in melanoma cells. Methods : Mice were divided into 3 experimental groups including vehicle (CON), SHJ extract and 5% minoxidil (MNXD, positive control)-treated group. SHJ was applied topically on the hair-shaved skin of C57BL/6 mice everyday for 15 days. The thickness and density of hair with a folliscope and morphometry of hair follicle with a H&E staining were monitored at last day. Also then, hair growth-associated gene expressions were measured by immunoblot assay. Results : The MNXD or SHJ-treated group promoted on hair growth compared to that of vehicle-treated group (CON). Hair density and thickness of MNXD or SHJ treated-group increased compared to that of vehicle application on the 15 days, respectively. Induction of insulin-like growth factor (IGF)-1 and vascular endothelial growth factor (VEGF) were also accelerated by application of SHJ extract compared to those of CON group. But expression of transforming growth factor (TGF)-${\beta}1$ decreased in SHJ treated-group compared to that of CON group. Furthermore, SHJ extract showed to increase melanin contents in a dose-dependent manner. Tyrosinase activity significantly increased in SHJ-treated group compared with CON group in dose-dependant manner. Conclusions : These results suggest that SHJ can be used as a component of cosmeceuticals for hair care via promoting growth and melanogenesis of hair.

Function and use of silkworm dpp gene (누에 유래의 dpp 유전자의 기능 및 유전체 연구를 통한 식의약용 신소재로서 활용)

  • Park, Seung Wong
    • Journal of Sericultural and Entomological Science
    • /
    • v.54 no.1_2
    • /
    • pp.1-5
    • /
    • 2016
  • The dpp gene originated from the silkworms is an important gene that is well conserved in the genome of humans, cattle, rodents, poultry and Drosophila. The dpp gene belonging to the TGF-beta (Transforming Growth Factor-beta) superfamily is known to play an important role in several developmental stages. The $TGF-{\beta}$ gene family is a genetically well-conserved and playing an important role gene family in various species such as determining cell proliferation and differentiation, apoptosis and cell fate. In this review, we have confirmed the following studies data. The recent studies on the silkworm dpp gene have confirmed for the first time the biological functions such as promoting osteogenesis activity. In addition, previous data shows that dpp have developmental functions such as morphogenetic materials at the blastophyllum stage, induction of the mesoblast at the late embryonic stage and involved in the proliferation and morphogenesis of imaginal disc in adult development. We found the splice variant of the dpp gene originated from the wildtype silkworm by using comparative genomics. It has provided important data for basic research based on genetics studies of these processes may promote a better understanding of evolution. Silkworm is a medicinal insect and is approved for its safety. It is used as a natural antibiotic for promoting growth as a medical material, a health functional food, and a feed additive. Therefore, it is necessary to present various data to obtain more value of functional insect.

Histopathologic Study and Expression of $TGF-{\beta}1$ of Choanal Polyp

  • Ahn, Byung-Hoon
    • The Korean Journal of Physiology and Pharmacology
    • /
    • v.5 no.4
    • /
    • pp.353-357
    • /
    • 2001
  • The pathogenesis of the nasal polyp is multifactorial and choanal polyps can be defined by its origin of genesis: antrochoanal (maxillochoanal), ethmochoanal and sphenochoanal polyp. Transforming growth $factor-{\beta}\;(TGF-{\beta})$ has various biologic activities, including the regulation of epithelial proliferation, the promotion of extracellular matrix formation and the induction of angiogenesis, hence closely related to pathogenesis of nasal polyp. Twenty cases of choanal polyps (13 antrochoanal, 4 ethmochoanal and 3 sphenochoanal polyps) were included in this study. Each polyp was subdivided into its origin, pedicle and choanal part. Hematoxylin and eosin stain for routine histopathology and immunohistochemistry were employed to detect expression of $TGF-{\beta}1.$ According to polyp type, edematous type is common at origin part and fibrous type at choanal part, and showed no difference at pedicle part in frequency. In ethmochoanal and sphenochoanal polyps, glandulocystic and edematous type is more common than fibrous type. $TGF-{\beta}1$ was expressed in epithelial cells, endothelial cells, eosinophils and lymphocytes. There was no different expression of $TGF-{\beta}1$ in each kind of choanal polyps and separate parts in each polyp. But histologic finding of choanal polyp is different between origin, pedicle and choanal part. Also infiltration of inflammatory cells including eosinophils has no difference between origin site. The expression of $TGF-{\beta}1$ was observed at all the choanal polyps and no difference between origin site and each portions was noted.

  • PDF

The Anti-Proliferation Effects and Its Mechanism of Bupleurum falcatum on Human Mesangial Cell (시호의 사구체 메산지움 세포 증식억제 효능 및 작용기전 연구)

  • Lee, Byung-Cheol;Ahn, Young-Min;Doo, Ho-Kyung;Ahn, Se-Young
    • The Journal of Internal Korean Medicine
    • /
    • v.25 no.4
    • /
    • pp.9-17
    • /
    • 2004
  • Objective : Mesangial cell proliferation and excessive accumulation of extracellular matrix (ECM) proteins is the common pathologic feature of glomerulosclerosis, and platelet-derived growth factor (PDGF) BB-chain, transforming growth factor betal $(TGF-{\beta}1)$, cyclin dependent kinases (CDK) and CDK inhibitors mediated in these pathophysiological processes. Bupleurum falcatum which is one of the most widely used components in traditional oriental medicines, has multiple pharmacological effects, such as antipyretic, analgesic, immune modulating, anti-inflammatory, anti-allergic, anti-thrombotic, anti-atherosclerotic, and antitussive effects. Methods : In this study, we evaluated the influence of Bupleurum falcatum on mesangial cell proliferation, DNA synthesis and expression of PDGF-BB chain, $TGF-{\beta}1$, CDKI, CDK2, CDK4, p21 and p27 in fetal bovine serum (FBS)-activated human mesangial cell. Results : Bupleurum falcatum reduced the mesangial cell proliferation and DNA synthesis more than control and captopril. And in the ELISA analysis of $TGF-{\beta}1$, and RT-PCR of PDGF-BB chain, CDK1, CDK2, CDK4, p21, and p27, Bupleurum falcatum inhibited the expression of $TGF-{\beta}1$ protein and PDGF-BB, CDK1, CDK2 gene and promoted that of p21 gene in a dose-dependent manner in comparing with control and captopril. Conclusions: These results suggest that Bupleurum falcatum may inhibit the mesangial cell proliferation and DNA synthesis by regulation of PDGF-BB and $TGF-{\beta}1$ expressions, and by modulation of CDK1, CDK2 and p21 expression.

  • PDF

Expression and Receptor Binding Activity of Fusion Protein from Transforming Growth Factor-${/beta}1$ and GFP

  • Yoon, Jun-Ho;Kim, Pyeung-Hyeun;Chun, Gie-Taek;Choi, Eui-Yul;Yie, Se-Won
    • Journal of Microbiology and Biotechnology
    • /
    • v.12 no.1
    • /
    • pp.65-70
    • /
    • 2002
  • A TGF-${\beta}1$/GFP monomeric fusion protein was cloned from pPK9A and pGFP-Cl plasmid by PCR amplification. The fusion protein was expressed in a $Bac-To-Bac^{TM}$ baculovirus expression system. A 45 kDa fusion protein was purified using an Ni-NTA column with 300 mM imidazol from a cell lysate infected with recombinant viruses for 72 h post-infection. The fusion protein cross-reacted with the commercial $TGF-{\beta}1$ polyclonal Ab as well as Ab raised against a precursor, monomeric $TGF-{\beta}1$, and GFP. The binding activity of the fusion protein with a $TGF-{\beta}1$ receptor was examined. Fluorescence was observed in Mv1Lu cells, yet not in insect cells treated with the fusion protein. No fluorescence was detected in Mv1Lu cells incubated with the fusion protein treated with Ab prior to the binding reaction, or with GFP alone, thereby indicating that the binding of the fusion protein was specific to $TGF-{\beta}1$ with a receptor.