• Herbal Formula Science
• /
• v.26 no.3
• /
• pp.183-193
• /
• 2018

Objectives : In Traditional Korean Medicine, Epimedium koreanum Nakai has diverse pharmacological activities to treat impotence, forgetfulness, cataract and exophthalmos. Present study investigated anti-fibrogenic effects of E. koreanum water extract (EKE) in hepatic stellate cells (HSCs). Methods : To study anti-fibrogenic effects of EKE, LX-2 cells, a human immortalized HSCs, were pre-treated with $3-300{\mu}g/mL$ of EKE, and then subsequently exposed to 5 ng/mL of transforming growth $factor-{\beta}1$ ($TGF-{\beta}1$). Expression level of ${\alpha}-smooth$ muscle actin was determined by immunoblot analysis. Phosphorylation of Smad, transactivation of Smad, and expression of plasminogen activator inhibitor-1 (PAI-1) were monitored to investigate the effect of EKE on $TGF-{\beta}1-mediated$ signaling pathway. Results : Up to $100{\mu}g/mL$, EKE did not show any cytotoxicity on LX-2 cells. Pre-treatment of EKE ($100{\mu}g/mL$) significantly inhibited ${\alpha}-smooth$ muscle actin expression induced by $TGF-{\beta}1$. In addition, EKE significantly decreased Smad2 and Smad3 phosphorylations, Smad binding element-driven luciferase activity and PAI-1 expression by $TGF-{\beta}1$. Of three flavonoid compounds found in EKE, only quercertin ($30{\mu}M$) attenuated $TGF-{\beta}1-mediated$ PAI-1 expression. Conclusion : These results suggest that EKE has an ability to suppress fibrogenic process in HSCs via inhibition of $TGF-{\beta}1/Smad$ signaling pathway.

• The Korean Journal of Physiology and Pharmacology
• /
• v.9 no.3
• /
• pp.159-164
• /
• 2005

Effects of antioxidants on the established nephropathy were investigated. The experimental nephropathy was induced in rats by intravenous injection of adriamycin (2 mg/kg). Six weeks later, when proteinuria was apparent, the rats were supplemented with N-acetylcysteine (NAC, 1 g/kg/day) in drinking water for additional 6 weeks. Glomerulosclerosis score and tubulointerstitial injury index were determined by light microscopy. Expression of transforming growth factor (TGF) ${\beta}1$ and laminin ${\beta}1$ was determined in the renal cortex by reverse transcription-polymerase chain reaction, Western blotting, immunohistochemistry, and immunogold electron microscopy. The adriamycin-induced proteinuria as well as the glomerulosclerosis and tubulointerstitial injury was ameliorated by the treatment with NAC. Adriamycin increased the expression of TGF ${\beta}1$ mRNA and protein, which was ameliorated by NAC. Although the expression of laminin ${\beta}1$ mRNA was increased, adriamycin did not significantly alter that of its protein. These results indicate that antioxidants ameliorate the established nephropathy in association with normalization of overexpressed TGF ${\beta}1$.

• Journal of the Korea Academia-Industrial cooperation Society
• /
• v.14 no.4
• /
• pp.1857-1862
• /
• 2013

Dermal fibroblasts produce the many components of the extracellular matrix (ECM) that are needed to maintain connective tissue integrity and repair tissue injuries. This study investigated the effects of Areca catechu extract (ACE) on dermal fibroblast cell activation. Cultured human dermal fibroblasts were treated with ACE, and then ECM production was determined by ELISA, Western blot and RT-PCR. ACE significantly accelerated the production of type 1 collagen, fibronectin, and transforming growth factor (TGF)-${\beta}1$ by ELISA and type 1 collagen by Western blot assay. ACE also increased the gene expression of COL1A1, TGF-${\beta}1$, keratinocyte growth factor (KGF) and insulin growth factor (IGF)-1. These results suggest that ACE has the potential to stimulate ECM production and that it might be suitable for maintaining skin texture.

• Biomolecules & Therapeutics
• /
• v.25 no.4
• /
• pp.417-426
• /
• 2017

4-O-methylhonokiol, a neolignan compound from Magnolia Officinalis, has been reported to have various biological activities including hair growth promoting effect. However, although transforming growth factor-${\beta}$ (TGF-${\beta}$) signal pathway has an essential role in the regression induction of hair growth, the effect of 4-O-methylhonokiol on the TGF-${\beta}$ signal pathway has not yet been elucidated. We thus examined the effect of 4-O-methylhonokiol on TGF-${\beta}$-induced canonical and noncanonical pathways in HaCaT human keratinocytes. When HaCaT cells were pretreated with 4-O-methylhonokiol, TGF-${\beta}1$-induced G1/G0 phase arrest and TGF-${\beta}1$-induced p21 expression were decreased. Moreover, 4-O-methylhonokiol inhibited nuclear translocation of Smad2/3, Smad4 and Sp1 in TGF-${\beta}1$-induced canonical pathway. We observed that ERK phosphorylation by TGF-${\beta}1$ was significantly attenuated by treatment with 4-O-methylhonokiol. 4-O-methylhonokiol inhibited TGF-${\beta}1$-induced reactive oxygen species (ROS) production and reduced the increase of NADPH oxidase 4 (NOX4) mRNA level in TGF-${\beta}1$-induced noncanonical pathway. These results indicate that 4-O-methylhonokiol could inhibit TGF-${\beta}1$-induced cell cycle arrest through inhibition of canonical and noncanonical pathways in human keratinocyte HaCaT cell and that 4-O-methylhonokiol might have protective action on TGF-${\beta}1$-induced cell cycle arrest.

• Proceedings of the Korean Society of Sericultural Science Conference
• /
• 2003.10a
• /
• pp.145-146
• /
• 2003

Overproduction of transforming growth factor (TGF)-$\beta$l has been implicated in the pathogenesis of fibrotic diseases. TGF-$\beta$l plays a crucial role in the accumulation of extracellular matrix (ECM) in human and experimental glomerular diseases. However, it remains unclear whether inhibition of TGF- $\beta$l overproduction would suppress TGF- $\beta$l induced ECM accumulation. To inhibit the overproduction of TGF- $\beta$l in experimental glomerulonephritis induced by anti-Thy 1.1 antibody, we introduced antisense oligodeoxynucleotides (ODN) fur TGF- $\beta$l into the nephritic kidney by the HVJ-liposome-mediated gene transfer method. (omitted)

• Clinical and Experimental Reproductive Medicine
• /
• v.48 no.2
• /
• pp.124-131
• /
• 2021

Objective: Approximately 30% of preeclamptic pregnancies exhibit abnormal liver function tests. We assessed liver injury-associated enzyme levels and circulating transforming growth factor beta (TGF-β) levels in an arginine vasopressin (AVP)-induced pregnant Sprague-Dawley rat model. Methods: Pregnant and non-pregnant Sprague-Dawley rats (n=24) received AVP (150 ng/hr) subcutaneously via mini-osmotic pumps for 18 days. Blood pressure was measured, urine samples were collected, and all animals were euthanized via isoflurane. Blood was collected to measure circulating levels of TGF-β1-3 isomers and liver injury enzymes in pregnant AVP (PAVP), pregnant saline (PS), non-pregnant AVP (NAVP), and non-pregnant saline (NS) rats. Results: The PAVP group showed significantly higher systolic and diastolic blood pressure than both saline-treated groups. The weight per pup was significantly lower in the AVP-treated group than in the saline group (p<0.05). Circulating TGF-β1-3 isomer levels were significantly higher in the PAVP rats than in the NS rats. However, similar TGF-β1 and TGF-β3 levels were noted in the PS and PAVP rats, while TGF-β2 levels were significantly higher in the PAVP rats. Circulating liver-type arginase-1 and 5'-nucleotidase levels were higher in the PAVP rats than in the saline group. Conclusion: This is the first study to demonstrate higher levels of TGF-β2, arginase, and 5'-nucleotidase activity in PAVP than in PS rats. AVP may cause vasoconstriction and increase peripheral resistance and blood pressure, thereby elevating TGF-β and inducing the preeclampsia-associated inflammatory response. Future studies should explore the mechanisms through which AVP dysregulates liver injury enzymes and TGF-β in pregnant rats.

• Clinical and Experimental Pediatrics
• /
• v.51 no.8
• /
• pp.879-885
• /
• 2008

Purpose : The human lung fibroblast may act as an immunomodulatory cell by providing pro-inflammatory cytokines and chemokines, which are important in airway remodeling. Vascular endothelial growth factor (VEGF) induces mucosal edema and angiogenesis. Thymus and activation regulated chemokine (TARC) induces selective migration of T helper 2 cells. We investigated whether human lung fibroblasts produced VEGF and TARC, and the effects were augmented with the co-culture of fibroblasts and human bronchial smooth muscle cells (HBSMC), and whether dexamethasone can inhibit the proliferation and the release of VEGF in lung fibroblasts. Methods : Human lung fibroblasts were cultured with and without HBSMC, growth-arrested in serum-deprived medium, and pretreated with dexamethasone for 16 hours. After 24-hour stimulation with platelet derived growth factor-BB (PDGF-BB) and/or transforming growth factor-${\beta}$ (TGF-${\beta}$), culture supernatant was harvested for assays of VEGF and TARC. Cell proliferation was assayed using BrdU cell proliferation ELISA kit. Results : 1) The release of VEGF was significantly increased after stimulation with TGF-${\beta}$, and its release was augmented when co-stimulated with PDGF and TGF-${\beta}$. 2) VEGF release induced by PDGF or TGF-${\beta}$ was inhibited by dexamethasone. 3) There was no synergistic effect on the release of VEGF when human lung fibroblasts were co-cultured with HBSMC. 4) Dexamethasone did not suppress human lung fibroblasts proliferations. 5) Neither TGF-${\beta}$ nor PDGF induced TARC release from lung fibroblasts. Conclusion : Human lung fibroblasts may modulate airway remodeling by release of VEGF, but they have no synergistic effects when co-cultured with HBSMC. Dexamethasone suppresses VEGF release, not proliferation of lung fibroblast.

• Microbiology and Biotechnology Letters
• /
• v.27 no.1
• /
• pp.28-34
• /
• 1999

Ganoderan (GAN), an immunomodulating ${\beta}$-glucan from mushroom Ganoderma lucidum, was evaluated for its ability to induce formation of nitric oxide (NO), tumor necrosis factor-${\alpha}$(TNF-${\alpha}$) and transforming growth factor (TGF-${\beta}$) from rat Kupffer cell in vitro. Hepatic macrophages activated by GAN significantly elevated concentration of NO and TNF-${\alpha}$ in cultured medium, but not significantly elevated that of TGF-${\beta}$. GAN-activated Kupffer cells secrete 14.9${\mu}$M (p<0.01) of NO and 2619.5${\rho}$g/ml (p<0.01) of TNF-${\alpha}$after 36hr of incubation at 37$^{\circ}C$. The results revealed that GAN enhanced 4-fold production of NO and 19 fold formation of TNF-${\alpha}$ compared to the control. The proliferation of GAN-activated Kupffer cells was inhibited as compared with its negative control. Comparing the activity among glucans derived from microorganisms, highly branched zymosan, glucomannan from Saccharomyces cerevisiae, significantly increased TNF-${\alpha}$ and NO production. These results indicate that the ${\beta}$-glucan from G. lucidum activates rat Kupffer cell and secretes NO and TNF-${\alpha}$. It also suggest that rat Kupffer cell posses certain receptor for ${\beta}$-anomeric glucan.

• Journal of Veterinary Science
• /
• v.19 no.6
• /
• pp.735-743
• /
• 2018

We investigated the effect of transforming growth factor beta 1 ($TGF-{\beta}1$) on equine hyaluronan synthase 2 (HAS2) gene expression and hyaluronan (HA) synthesis in culture models of articular chondrocytes. Equine chondrocytes were treated with $TGF-{\beta}1$ at different concentrations and times in monolayer cultures. In three-dimensional cultures, chondrocyte-seeded gelatin scaffolds were cultured in chondrogenic media containing 10 ng/mL of $TGF-{\beta}1$. The amounts of HA in conditioned media and in scaffolds were determined by enzyme-linked immunosorbent assays. HAS2 mRNA expression was analyzed by semi-quantitative reverse transcription polymerase chain reaction. The uronic acid content and DNA content of the scaffolds were measured by using colorimetric and Hoechst 33258 assays, respectively. Cell proliferation was evaluated by using the alamarBlue assay. Scanning electron microscopy (SEM), histology, and immunohistochemistry were used for microscopic analysis of the samples. The upregulation of HAS2 mRNA levels by $TGF-{\beta}1$ stimulation was dose and time dependent. $TGF-{\beta}1$ was shown to enhance HA and uronic acid content in the scaffolds. Cell proliferation and DNA content were significantly lower in $TGF-{\beta}1$ treatments. SEM and histological results revealed the formation of a cartilaginous-like extracellular matrix in the $TGF-{\beta}1$-treated scaffolds. Together, our results suggest that $TGF-{\beta}1$ has a stimulatory effect on equine chondrocytes, enhancing HA synthesis and promoting cartilage matrix generation.

• Archives of Pharmacal Research
• /
• v.22 no.1
• /
• pp.1-8
• /
• 1999

Transforming growth factor-$\beta$ (TGF-$\beta$) is the prototypical multifunctional cytokine, participating in the regulation of vital cellular activities such as proliferation and differentiations as well as a number of basic physiological functions. The effects of TGF-$\beta$ are critically dependent on the expression and distribution of a family of TGF-$\beta$ receptors, the TGF-$\beta$ types I, II, and III. It is now known that a wide variety of human pathology can be caused by aberrant expression and function of these receptors. the coding sequence of the type II receptor (RII) appears to render it uniquely susceptible to DNA replication errors in the course of normal cell division. By virtue of its key role in the regulation of cell proliferation, TGF-$\beta$ RII should be considered as a tumor suppressor gene. High levels of mutation in the TGF-$\beta$ RII gene have been observed in a wide range of primarily epithelial malignancies, including colon and gastric cancer. It appears likely that mutation of the TGF-$\beta$ RII gene may be a very critical step in the pathway of carcinogenesis.