• Journal of Physiology & Pathology in Korean Medicine
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• v.23 no.5
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• pp.986-992
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• 2009

Type I interferons (IFNs) are critical mediators of the innate immune system to defend viral infection. Interferon regulatory factor (IRF) and signal transducer and activator of transcription (STAT) play critical roles in type I IFN production in response to viral infection. Luteolin is natural polyphenolic compounds that have anti-inflammatory, cytoprotective and anti-carcinogenic effects. However, the mechanism of action and impact of luteolin on innate immunity is still unknown. In this study, we examined the effects of luteolin on the lipopolysacchride (LPS)-induced inflammatory responses. Luteolin inhibited Type I IFNs expression of mRNA and increased interleukin(IL)-10 expression of mRNA. Next, we examined the protective effects of IL-10 using IL-10 neutralizing antibody (IL-10NA). Blockade of IL-10 action didn't cause a significant reduction of Type I IFNs than LPS-induced luteolin pretreatment. Pretreatment of luteolin inhibited the level of IRF-1, and IRF-7 mRNA and the nuclear translocation of IRF-3. Also, luteolin reduced the activation of STAT - 1, 3. Theses results suggest that luteolin inhibits LPS-induced the production of Type I IFNS by both IRFs and STATs not IL-10 and may be a beneficial drug for the treatment of inflammatory disease.

• Journal of Oral Medicine and Pain
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• v.26 no.1
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• pp.39-50
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• 2001

In order to investigate the effect of Transforming growth factor ${\beta}1$(below TGF-${\beta}1$) and osteogenic protein-1(below Op-1) onto the myogenic differentiation, C2C12 satellite myoblastic cell line was cultured and treated with both growth factors. At first morphological changes with microscopical examination were examined, and isolated total RNA to analyse mRNA expression of bone marker proteins, muscle regulatory proteins, TGF-${\beta}$ receptor and their ligands by Northern blot analysis. And cellular proliferative inducibility of both growth factors was also tested to C2C12 cells. Incubating the cell with $5ng/m{\ell}$ of TGF-${\beta}1$ until 4 days almost inhibited multinucleated myotube formation expressing muscular regulatory proteins, and induced decreasing Id proteins. However, no osteoblastic phenotypes was induced by TGF-${\beta}1$ in C2C12 cells. The mRNA expression of TGF-${\beta}$ receptors with TGF-${\beta}1$ was conversed after 48 hours cultured. Type I TGF-${\beta}$ receptor was seemed to play a role in negative signalling for inhibition of myogenic differentiation. OP-1 dose dependently induced ALP activity, osteopontine production and bone sialoprotein production at concentrations above $100ng/m{\ell}$ and osteocalcin production at concentrations above $300ng/m{\ell}$. The concentration of OP-1 required to induce these osteoblastic phenotypes was the same as that required to almost completely inhibit myotube formation. Incubation with above $100ng/m{\ell}$ OP-1 suppressed the expression of mRNA for muscular egulatory proteins from 2 days after incubation. Expression of Id-1, 2, 3 mRNA were stimulated by OP-1 at concentration above $300ng/m{\ell}$. When C2C12 cells were treated with both growth factors, TGF-${\beta}1$ potentiated the inhibitory effect of OP-1 on myotube formation and expression of mRNA for myogenin at 12 days. And TGF-${\beta}1$ reduced osteocalcin and bone sialoprotein production induced by OP-1 at 12 days in C2C12 cells. Both growth factor had no mitogenic effect. These results indicate that OP-1 converts the differentiation pathway of C2C12 myoblasts into that of osteoblastic lineage cells and it's not heritable, but TGF-${\beta}1$ does not and has reversible inhibitory activity on the myogenic differentiation. TGF-${\beta}1$ and OP-1 play a role in myogenic differentiation via different mechanism between them.

• Clinical and Experimental Reproductive Medicine
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• v.23 no.3
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• pp.269-275
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• 1996

Biosynthesis and secretion of anterior pituitary hormones are under the control of specific hypothalamic stimulatory and inhibitory factors. Among them, Growth Hormone Releasing Hormone (GHRH) is the major stimulator of pituitary somatotrophs activating GH gene expression and secretion. Human GHRH is a polypeptide of 44 amino acids initially isolated from pancreatic tumors, and the gene for the hypothalamic form of GHRH is organized into 5 exons spanning over 10 kilobases (kb) on genomic DNA and encodes a messenger RNA of 700-750 nucleotides. Several neuropeptides classically associated with the hypothalamus have been found in the extrahypothalamic regions, suggesting the existence of novel sources, targets and functions. GHRH-like immunoreactivity has been found in several peripheral sites, including placenta, testis, and ovary, indicating that GHRH may also have regulatory roles in peripheral reproductive organs. Furthermore, higher molecular weight forms of the GHRH transcripts were identified from these organs (1.75 kb in testis; 1.75 and >3 kb in ovary). These tissue-specific expression of GHRH gene suggest the existence of unique regulatory mechanism of GHRH expression and function in these organs. In fact, placenta-specific and testis-specific promoters for GHRH transcripts which are located in about 10 kb upstream region of hypothalamic promoter were reported. The use of unique promoters in extrahypothalamic sites could be refered in a different control of GHRH gene and different functions of the translated products in these tissues. Somatotrophs and lactotrophs have been thought to be derived from a common bipotential progenitor, the somatolactotrophs, which give origins to either phenotypes. Although the precise mechanism responsible for the lactotroph differentiation in the anterior pituitary gland has not been yet clalified, there are several candidators for the generation of lactotrophs. In human, the presence of GHRH peptides with different size from authentic hypothalamic form in the normal anterior pituitary and several types of adenoma were demonstrated. Recently our group found the existence of immunoreactive GHRH and its transcript from the normal rat anterior pituitary (gonadotroph> somatotroph> lactotroph), and the GHRH treatment evoked the increased proliferation rate of anterior pituitary cells in vitro. The transgenic mouse models clearly shown that GHRH or NGF overexpression by anterior pituitary cells induced development of pituitary hyperplasia and adenomas particularly GH-oma and prolactinoma. Taken together, we hypothesize that the pituitary GHRH could serve not only as a modulator of hormone secretion but as a paracrine or autocrine regulator of anterior pituitary cell proliferation and differentiation. Interestingly enough, the expression of Pit-1 homeobox gene (the POU class transcription factor) was confined to somatotrophs, lactotrophs and somatolactotrophs in which GHRH receptors are expressed commonly. Concerning the mechanism of somatolactotroph and lactotroph differentiation in the anterior pituitary, we have focused following two possibilities; (1) changes in the relative levels or interactions of both hypothalamic and intrapituitary factors such as dopamine, VIP, somatostatin, NGF and GHRH; (2) alterations of GHRH-GHRH receptor signaling and Pit-1 activity may be the cause of lactotroph differentiation or pituitary hyperplasia and adenoma formation. Extensive further studies will be necessary to solve these complicated questions.

• Journal of Life Science
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• v.31 no.9
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• pp.796-805
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• 2021

Hepatic endoplasmic reticulum (ER) stress contributes to the development of steatosis and insulin resistance. The components of unfolded protein response (UPR) regulate lipid metabolism. Recent studies have reported an association between ER stress and aberrant cellular lipid control; moreover, research has confirmed the involvement of sterol regulatory element-binding proteins (SREBPs)-the central regulators of lipid metabolism-in the process. However, the exact role of SREBPs in controlling lipid metabolism during ER stress and its contribution to fatty liver disease remain unknown. Here, we show that SREBP-1c deficiency protects against ER stress-induced hepatic steatosis in mice by regulating UPR, inflammation, and fatty acid oxidation. SREBP-1c directly regulated inositol-requiring kinase 1α (IRE1α) expression and mediated ER stress-induced tumor necrosis factor-α activation, leading to a reduction in expression of peroxisome proliferator-activated receptor γ coactivator 1-α and subsequent impairment of fatty acid oxidation. However, the genetic ablation of SREBP-1c prevented these events, alleviating hepatic inflammation and steatosis. Although the mechanism by which SREBP-1c deficiency prevents ER stress-induced inflammatory signaling remains to be elucidated, alteration of the IRE1α signal in SREBP-1c-depleted Kupffer cells might be involved in the signaling. Overall, the results suggest that SREBP-1c plays a crucial role in the regulation of UPR and inflammation in ER stress-induced hepatic steatosis.

• Animal Bioscience
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• v.35 no.7
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• pp.1010-1020
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• 2022

Objective: The experiment was conducted to evaluate the effects of maternal undernutrition during late pregnancy on the expressions of genes involved in growth and development in ovine fetal perirenal brown adipose tissue (BAT). Methods: Eighteen ewes with singleton fetuses were allocated to three groups at day 90 of pregnancy: restricted group 1 (RG1, 0.33 MJ metabolisable energy [ME]/kg body weight [BW]^0.75/d, n = 6), restricted group 2 (RG2, 0.18 MJ ME/kg BW^0.75/d, n = 6), and a control group (CG, ad libitum, 0.67 MJ ME/kg BW^0.75/d, n = 6). The fetuses were removed at day 140 of pregnancy. All data were analyzed by using the analysis of variance procedure. Results: The perirenal fat weight (p = 0.0077) and perirenal fat growth rate (p = 0.0074) were reduced in RG2 compared to CG. In fetal perirenal BAT, the protein level of uncoupling protein 1 (UCP1) (p = 0.0001) was lower in RG1 and RG2 compared with CG and UCP1 mRNA expression (p = 0.0265) was decreased in RG2. The protein level of myogenic factor 5 (Myf5) was also decreased in RG2 (p = 0.0001). In addition, mRNA expressions of CyclinA (p = 0.0109), CyclinB (p = 0.0019), CyclinD (p = 0.0015), cyclin-dependent kinase 1 (CDK1) (p = 0.0001), E2F transcription factor 1 (E2F1) (p = 0.0323), E2F4 (p = 0.0101), and E2F5 (p = 0.0018) were lower in RG1 and RG2. There were decreased protein expression of peroxisome proliferator-activated receptor-γ (PPARγ) (p = 0.0043) and mRNA expression of CCAAT/enhancer-binding protein-α (C/EBPα) (p = 0.0307) in RG2 and decreased PPARγ mRNA expression (p = 0.0008) and C/EBPα protein expression (p = 0.0015) in both RG2 and RG1. Furthermore, mRNA expression of bone morphogenetic protein 4 (BMP4) (p = 0.0083) and BMP7 (p = 0.0330) decreased in RG2 and peroxisome proliferator-activated receptor co-activator-1α (PGC-1α) reduced in RG2 and RG1. Conclusion: Our observations support that repression of regulatory factors promoting differentiation and development results in the inhibition of BAT maturation in fetal perirenal fat during late pregnancy with maternal undernutrition.

• Journal of Sericultural and Entomological Science
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• v.51 no.2
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• pp.99-106
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• 2013

The purpose of this study is to investigate the effects of supplementation of mulberry powder, mulberry extract and silkworm powder during the 8 weeks of resistance exercise on Androgen receptor(AR) mRNA and Myogenic regulatory factors(MRFs) expression of rats muscle. Fifty males, Sprague-Dawley rat, were randomly divided into 5 groups: CON(control group, n = 10), REG(resistance exercise group, n = 10), MP REG(mulberry powder intake and resistance exercise group, n = 10), ME REG(mulberry extract intake and resistance exercise group, n = 10) and SP REG(silkworm powder intake and resistance exercise group, n = 10). After climbing the ladder without weights during the 1 week of adaptation period, the rats in the resistance exercise group were trained to climb a 0.98-m vertical(80 degree incline) ladder with weights in their tail during 7 weeks(10 times each day, 2 days per week). After exercise, the skeletal muscle was extracted from the flexor hallucis longus. After separating the total ribonucleic acid (RNA) of each group, quantitative polymerase chain reaction was used to analyze RNA quantitatively. AR mRNA and MRFs expression revealed that all of the treated groups had significantly difference. AR mRNA expression increased in ME REG $6.24{\pm}1.85$ and SP REG $9.68{\pm}0.28$ fold compared to CON. Myod mRNA expression increased in MP REG $6.04{\pm}0.47$, ME REG $4.31{\pm}1.58$ and SP REG $8.11{\pm}0.57$ fold compared to CON. And myogenin mRNA expression increased in MP REG $4.11{\pm}0.42$, ME REG $4.12{\pm}0.45$ and SP REG $6.50{\pm}0.61$ fold compared to CON. In conclusion, during the resistance exercise, providing mulberry and silkworm gives positive effect on AR mRNA and MRFs expression increase.

• The Korean Journal of Zoology
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• v.39 no.3
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• pp.317-324
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• 1996

Osteoclast has been known as a primary responsible cell for the bone resorption. The activation of osteoclast, therefore, may be the key event in the regulation of bone growth and remodeling. Various factors were reported to have influence on the resorbing activity of osteoclast in organ culture. Among those factors, transforming growth factor-$\beta$ (TGF-$\beta$) has been known to have a profound effect on bone metabolism. Since a large amount of TGF-$\beta$ presents in bone tissue, it may be important for the understanding the regulatory mechanism of bone resorption to elucidate the effect of TGF-$\beta$ on the osteoclast. We have reported the dlsaggregated chick embryonic osteoclast culture as an useful assay method for determining the resorption activity of osteoclast. In this culture, we found that TGF-$\beta$ significantly enhaced the osteoclastic bone resorption activity. We also found that the timulatory effect seemed to be an indirect one that is mediated by other cells. As nordihydroguaiaretic acid significantly inhibited the TGF-$\beta$1-induced osteoclastic bone resorption, we suggest that the lipoxygenase derivative of arachidonic acid may participate in the action of TGF-$\beta$ as a paracrine or an autocrine mediator.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.18
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• pp.8579-8587
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• 2016

Background: The molecular mechanisms linking breast cancer progression and inflammation still remain obscure. The aim of the present study was to investigate the possible association of angiopoeitin like protein 4 (ANGPTL4) and its regulatory factor, hypoxia inducible factor-$1{\alpha}$ (HIF-$1{\alpha}$), with the inflammatory markers nuclear factor kappa B/p65 (NF-${\kappa}B$/P65) and interleukin-1 beta (IL-$1{\beta}$) in order to evaluate their role in inflammation associated breast cancer progression. Materials and Methods: Angiopoietin-like protein 4 (ANGPTL4) mRNA expressions were evaluated using quantitative real time PCR and its protein expression by immunohistochemistry. DNA binding activity of NF-${\kappa}B$/P65 was evaluated by transcription factor binding immunoassay. Serum levels of ANGPTL4, HIF-$1{\alpha}$ and IL-$1{\beta}$ were immunoassayed. Tumor clinico-pathological features were investigated. Results: ANGPTL4 mRNA expressions and serum levels were significantly higher in high grade breast carcinoma ($1.47{\pm}0.31$ and $184.98{\pm}18.18$, respectively) compared to low grade carcinoma ($1.21{\pm}0.32$ and $171.76{\pm}7.58$, respectively) and controls ($0.70{\pm}0.02$ and $65.34{\pm}6.41$, respectively), (p<0.05). Also, ANGPTL4 high/moderate protein expression was positively correlated with tumor clinico-pathological features. In addition, serum levels of HIF-$1{\alpha}$ and IL-$1{\beta}$ as well as NF-${\kappa}B$/P65 DNA binding activity were significantly higher in high grade breast carcinoma ($148.54{\pm}14.20$, $0.79{\pm}0.03$ and $247.13{\pm}44.35$ respectively) than their values in low grade carcinoma ( $139.14{\pm}5.83$, $0.34{\pm}0.02$ and $184.23{\pm}37.75$, respectively) and controls ($33.95{\pm}3.11$, $0.11{\pm}0.02$ and $7.83{\pm}0.92$, respectively), (p<0.001). Conclusion: ANGPTL4 high serum levels and tissue expressions in advanced grade breast cancer, in addition to its positive correlation with tumor clinico-pathological features and HIF-$1{\alpha}$ could highlight its role as one of the signaling factors involved in breast cancer progression. Moreover, novel correlations were found between ANGPTL4 and the inflammatory markers, IL-$1{\beta}$ and NF-${\kappa}B$/p65, in breast cancer, which may emphasize the utility of these markers as potential tools for understanding interactions for axes of carcinogenesis and inflammation contributed for cancer progression. It is thus hoped that the findings reported here would assist in the development of new breast cancer management strategies that would promote patients' quality of life and ultimately improve clinical outcomes. However, large-scale studies are needed to verify these results.

• Journal of the korean academy of Pediatric Dentistry
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• v.27 no.2
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• pp.300-308
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• 2000

The Fibroblast growth factors(FGFs) plays an important role in the control of osteogenesis during skeletal development. Especially, FGF-2 is a potent mesodermal inducer during embryogenesis and FGF receptors (FGFRs) messages are strongly expressed in developing bones. In this study, we investigated the effect of bFGF on osteopontin(OPN) gene expression in ST-2 cells and tried to elucidate the mechanism of its stimulatory effects. The obtain results were as follows; The treatment of bFGF(1ng/ml) upregulates OPN, fibronectin mRNA levels and downregulates type I collagen mRNA levels. But, there was no remarkable difference in alkaline phosphatase mRNA levels between two groups. The OPN gene expression increased in a dose-dependent manner up to 10ng/ml and OPN gene began to occur at around 3h with continuous increase up to 24h then decreased to basal level at 48h. 30 minutues pretreatment with cycloheximide (500ng/ml), a protein synthesis inhibitor, prior to addition bFGF resulted in blocking bFGF induced OPN expression. These results suggest that bFGF increased the level of OPN mRNA in a dose and time-dependent manner via the synthesis of certain transcriptional regulatory proteins.

• Asian-Australasian Journal of Animal Sciences
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• v.22 no.5
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• pp.636-642
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• 2009

The corpus luteum (CL) is a transient endocrine gland that produces progesterone, a product required for the establishment and maintenance of pregnancy. In the absence of pregnancy, the production of progesterone in the CL decreases and the structure itself regresses in size. The life span and function of the CL are regulated by complex interactions between stimulatory (luteotrophic) and inhibitory (luteolytic) mediators. When an ovum is released from a mature follicle, angiogenesis and rapid growth of follicular cells form the CL. The purpose of the present study was to determine whether steroidogenesis, proliferation, and hypoxiarelated proteins are expressed in caprine CL. The expression of proliferating cell nuclear antigen (PCNA), vascular endothelial growth factor (VEGF), and hypoxia-inducible factor $1{\alpha}$ (HIF-$1{\alpha}$) were determined in caprine CL during the estrous cycle. Cytochrome P450 side chain cleavage protein did not vary significantly during the estrous cycle; however, there was an increased expression of $3{\beta}$ -hydroxysteroid dehydrogenase in the early and middle stages, which rapidly decreased in the late stage. The same observations were made with respect to steroidogenic acute regulatory protein. Variations in progesterone content and expression of PCNA, HIF-$1{\alpha}$, and VEGF were consistent with this result. Thus, the steroidogenic proteins, PCNA, HIF-$1{\alpha}$, and VEGF in caprine CL are dependent on the stage of the estrous cycle.