• Title/Summary/Keyword: Igf2

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Cashmere growth control in Liaoning cashmere goat by ovarian carcinoma immunoreactive antigen-like protein 2 and decorin genes

  • Jin, Mei;Zhang, Jun-yan;Chu, Ming-xing;Piao, Jun;Piao, Jing-ai;Zhao, Feng-qin
    • Asian-Australasian Journal of Animal Sciences
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    • v.31 no.5
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    • pp.650-657
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    • 2018
  • Objective: The study investigated the biological functions and mechanisms for controlling cashmere growth of Liaoning cashmere goat by ovarian carcinoma immunoreactive antigen-like protein 2 (OCIAD2) and decorin (DCN) genes. Methods: cDNA library of Liaoning cashmere goat was constructed in early stages. OCIAD2 and DCN genes related to cashmere growth were identified by homology analysis comparison. The expression location of OCIAD2 and DCN genes in primary and secondary hair follicles (SF) was performed using in situ hybridization. The expression of OCIAD2 and DCN genes in primary and SF was performed using real-time polymerase chain reaction (PCR). Results: In situ hybridization revealed that OCIAD2 and DCN were expressed in the inner root sheath of Liaoning cashmere goat hair follicles. Real-time quantitative PCR showed that these genes were highly expressed in SF during anagen, while these genes were highly expressed in primary hair follicle in catagen phase. Melatonin (MT) inhibited the expression of OCIAD2 and promoted the expression of DCN. Insulin-like growth factors-1 (IGF-1) inhibited the expression of OCIAD2 and DCN, while fibroblast growth factors 5 (FGF5) promoted the expression of these genes. MT and IGF-1 promoted OCIAD2 synergistically, while MT and FGF5 inhibited the genes simultaneously. MT+IGF-1/MT+FGF5 inhibited DCN gene. RNAi technology showed that OCIAD2 expression was promoted, while that of DCN was inhibited. Conclusion: Activation of bone morphogenetic protein (BMP) signaling pathway up-regulated OCIAD2 expression and stimulated SF to control cell proliferation. DCN gene affected hair follicle morphogenesis and periodic changes by promoting transforming growth $factor-{\beta}$ ($TGF-{\beta}$) and BMP signaling pathways. OCIAD2 and DCN genes have opposite effects on $TGF-{\beta}$ signaling pathway and inhibit each other to affect the hair growth.

Hair follicle development and related gene and protein expression of skins in Rex rabbits during the first 8 weeks of life

  • Wu, Zhenyu;Sun, Liangzhan;Liu, Gongyan;Liu, Hongli;Liu, Hanzhong;Yu, Zhiju;Xu, Shuang;Li, Fuchang;Qin, Yinghe
    • Asian-Australasian Journal of Animal Sciences
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    • v.32 no.4
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    • pp.477-484
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    • 2019
  • Objective: We aimed to observe hair follicle (HF) development in the dorsal skin and elucidate the expression patterns of genes and proteins related to skin and HF development in Rex rabbits from birth to 8 weeks of age. Methods: Whole-skin samples were obtained from the backs of Rex rabbits at 0, 2, 4, 6, and 8 weeks of age, the morphological development of primary and secondary HFs was observed, and the gene transcript levels of insulin-like growth factor-I (IGF-I), epidermal growth factor (EGF), bone morphogenetic protein 2 (BMP2), transforming growth factor ${\beta}-1$, 2, and 3 ($TGF{\beta}-1$, $TGF{\beta}-2$, and $TGF{\beta}-3$) were examined using quantitative real-time polymerase chain reaction (PCR). Additionally, Wnt family member 10b (Wnt10b) and ${\beta}$-Catenin gene and protein expression were examined by quantitative real-time PCR and western blot, respectively. Results: The results showed significant changes in the differentiation of primary and secondary HFs in Rex rabbits during their first 8 weeks of life. The IGF-I, EGF, $TGF{\beta}-2$, and $TGF{\beta}-3$ transcript levels in the rabbits were significantly lower at 2 weeks of age than at birth and gradually increased thereafter, while the BMP2 and $TGF{\beta}-1$ transcript levels at 2 weeks of age were significantly higher than those at birth and gradually decreased thereafter. ${\beta}$-Catenin gene expression was also significantly affected by age, while the Wnt10b transcript level was not. However, the Wnt10b and ${\beta}$-catenin protein expression levels were the lowest at 2 and 4 weeks of age. Conclusion: Our data showed that a series of changes in HFs in dorsal skin occurred during the first 8 weeks. Many genes, such as IGF-I, EGF, BMP2, $TGF{\beta}-1$, $TGF{\beta}-2$, $TGF{\beta}-3$, and ${\beta}$-Catenin, participated in this process, and the related proteins Wnt10b and ${\beta}$-Catenin in skin were also affected by age.

Regulatory Mechanism of Insulin-Like Growth Factor Binding Protein-3 in Non-Small Cell Lung Cancer (비소세포성 폐암에서 인슐린 양 성장 인자 결합 단백질-3의 발현 조절 기전)

  • Chang, Yoon Soo;Lee, Ho-Young;Kim, Young Sam;Kim, Hyung Jung;Chang, Joon;Ahn, Chul Min;Kim, Sung Kyu;Kim, Se Kyu
    • Tuberculosis and Respiratory Diseases
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    • v.56 no.5
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    • pp.465-484
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    • 2004
  • Background : Insulin-like growth factor (IGF)-binding protein-3 (IGFBP-3) inhibits the proliferation of non-small cell lung cancer (NSCLC) cells by inducing apoptosis. Methods : In this study, we investigated whether hypermethylation of IGFBP-3 promoter play an important role in the loss of IGFBP-3 expression in NSCLC. We also studied the mechanisms that mediate the silencing of IGFBP-3 expression in the cell lines which have hypermethylated IGFBP-3 promoter. Results : The IGFBP-3 promoter has hypermethylation in 7 of 15 (46.7%) NSCLC cell lines and 16 (69.7%) of 23, 7 (77.8%) of 9, 4 (80%) of 5, 4 (66.7 %) of 6, and 6 (100%) of 6 tumor specimens from patients with stage I, II, IIIA, IIIB, and IV NSCLC, respectively. The methylation status correlated with the level of protein and mRNA in NSCLC cell lines. Expression of IGFBP-3 was restored by the demethylating agent 5'-aza-2'-deoxycytidine (5'-aza-dC) in a subset of NSCLC cell lines. The Sp-1/ Sp-3 binding element in the IGFBP-3 promoter, important for promoter activity, was methylated in the NSCLC cell lines which have reduced IGFBP-3 expression and the methylation of this element suppressed the binding of the Sp-1 transcription factor. A ChIP assay showed that the methylation status of the IGFBP-3 promoter influenced the binding of Sp-1, methyl-CpG binding protein-2 (MeCP2), and histone deacetylase (HDAC) to Sp-1/Sp-3 binding element, which were reversed by by 5'-aza-dC. In vitro methylation of the IGFBP-3 promoter containing the Sp-1/Sp-3 binding element significantly reduced promoter activity, which was further suppressed by the overexpression of MeCP2. This reduction in activity was rescued by 5'-aza-dC. Conclusion : These findings indicate that hypermethylation of the IGFBP-3 promoter is one mechanism by which IGFBP-3 expression is silenced and MeCP2, with recruitment of HDAC, may play a role in silencing of IGFBP-3 expression. The frequency of this abnormality is also associated with advanced stages among the patients with NSCLC, suggesting that IGFBP-3 plays an important role in lung carcinogenesis/progression and that the promoter methylation status of IGFBP-3 may be a marker for early molecular detection and/or for monitoring chemoprevention efforts.

A Case of Acromegaly Associated with Lung and Gastric Cancer (폐암과 위암을 동반한 말단비대증 1예)

  • Kim, Jin Soo;Kil, Uk Hyun;Song, Do Seon;Yang, Hong Jun;Lee, Hyeug;Huh, Min;Kim, Jeong Pyo;Kwon, Soon Seog;Kim, Young Kyoon;Kim, Kwan Hyoung;Moon, Hwa Sik;Song, Jeong Sup;Park, Sung Hak;Ahn, Joong Hyun
    • Tuberculosis and Respiratory Diseases
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    • v.59 no.2
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    • pp.198-203
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    • 2005
  • Patients with acromegaly have high incidence of benign or malignant neoplasia than general population. Around fifteen percent of the deaths reported in acromegaly are attributable to malignancy of cancer. On the whole, mortality in acromegaly has been shown to be correlated with the degree of growth hormone (GH) control. Especially, the levels of insulin like growth factor-1 (IGF-1) may be higher in neoplasm, but there is no clear evidence to prove that tumor development is triggered by IGF-1 in acromegaly. Henceforth, we report a case of acromegaly associated with lung and gastric cancer in a 58-year-old man, suggesting the possible carcinogenic role of IGF-1.

옻나무 유래 Flavonoid처리가 흰쥐 Leydig 세포의 체외배양에서 Testosterone분비에 미치는 영향

  • 성환후;최선호;민관식;장유민;나천수;정일정
    • Proceedings of the KSAR Conference
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    • 2001.03a
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    • pp.80-80
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    • 2001
  • 옻나무 유래 Flavonoid(F)는 항암 효과, 숙취해소 등의 효능이 있으며, 신장의 기능을 촉진하고 생식에도 영향을 준다고 알려져 있다. 그 주성분으로는 fustin, fisetin, sulfuretin, butein으로 추정되고 있다. 본 연구팀의 예비실험에서 성숙 흰쥐에게 F를 30일간 5mg씩 구강투여 하여 정소 중량 및 혈액 내 Testosterone 농도를 분석한 결과, 정소 중량이 증가되고 혈중 Testosterone의 농도도 대조구에 비해 유의적으로 높은 결과를 얻었다. 이에 본 연구의 목적은 옻나무 유래 F가 성숙 수컷 횐쥐의 생식 기능에 직접 미치는 영향을 알아보고자, 흰쥐 Leydig 세포를 분리, 회수하여 체외배양에서 Testosterone농도를 조사하였다. SD계 흰쥐(약 12주령, 체중 250g 전후)의 정소를 적출 한 후, Leydig 세포를 회수하기 위해 0.25% collagenase용액에 넣어 34$^{\circ}C$에서 15분간 진탕 수조에서 배양하였다. 배양된 정소조직은 D-MEM 배양액(10% FCS와 antibiotics 첨가)으로 2~3회 세척한 후 세포 수를 1$\times$$10^{6}$ cells/$m\ell$/well로 분주하여, F(20, 40, 80, 160ng), IGF-I(50, 100ng) 와 LH(10, 100ng) 용량별 각각 첨가하여 배양하였다. 각 처리 후, 배양시간(3, 6, 12, 24, 36시간)에 따라 배양액을 회수하여 COAT-A-COUNT(DPC, USA) kit를 이용하여 RIA방법에 의해 Testosterone을 분석한 결과는 다음과 같다. 대조구 Leydig 세포를 36시간까지 체외 배양하여 Testosterone의 농도를 조사한 결과, 24시간 배양구가 가장 높은 농도를 나타내었다. F를 단독 첨가하여 12시간 배양한 실험에서 F 80ng 첨가구에서 유의적으로 높은 농도를 보였다. LH 10ng 및 100ng 첨가구의 시간별 변화로는, LH 10ng 첨가구에서는 6~12시간 이후, LH 100ng 첨가구에서는 3~6시간 사이에서 유의적인 증가를 보였다. 또한, LH 10ng 첨가 실험에서는 LH 10ng+F 40ng에서 12시간 배양 시, 유의적으로 높은 Testosterone 분비를 확인하였으며, LH 100ng을 첨가하여 3시간 배양 시는 각 처리구 마다 높은 유의적 차이를 보였다. 한편, GH에 관여하는 IGF-I 첨가효과를 비교 검토한 결과, LH 100ng+IGF-I 100ng, 6시간 배양구에서 유의적으로 높게 나타내었다. 이상의 결과로, F 단독 처리 시의 적정량은 약 80ng이며, 흰쥐 정소 Leydig 세포의 Testosterone분비를 촉진하는 작용을 하는 것으로 사료되며, 특히 LH+F구에서 Testosterone분비를 더욱 향상시킴으로써 정소 Leydig 세포의 Androgen 생성을 촉진시키는 역할이 있는 것으로 보여진다 따라서 옻나무 유래 F는 포유동물의 생식기능에 중요하게 작용하는 것으로 사료된다.

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Transcriptional Properties of the BMP, $TGF-\beta$, RTK, Wnt, Hh, Notch, and JAK/STAT Signaling Molecules in Mouse Embryonic Stem Cells

  • Rho Jeung-Yon;Bae Gab-Yong;Chae Jung-Il;Yu Kweon;Koo Deog-Bon;Lee Kyung-Kwang;Han Yong-Mahn
    • Reproductive and Developmental Biology
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    • v.30 no.2
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    • pp.143-156
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    • 2006
  • Major characteristics of embryonic stem cells (ESCs) are sustaining of sternness and pluripotency by self-renewal. In this report, transcriptional profiles of the molecules in the developmentally important signaling pathways including Wnt, BMP4, $TGF-\beta$, RTK, Hh, Notch, and JAK/STAT signaling pathways were investigated to understand the self-renewal of mouse ESCs (mESCs), J1 line, and compared with the NIH3T3 cell line and mouse embryonic fibroblast (MEF) cells as controls. In the Wnt signaling pathway, the expression of Wnt3 was seen widely in mESCs, suggesting that the ligand may be an important regulator for self-renewal in mESCs. In the Hh signaling pathway, the expression of Gli and N-myc were observed extensively in mESCs, whereas the expression levels of in a Shh was low, suggesting that intracellular molecules may be essential for the self-renewal of mESCs. IGF-I, IGF-II, IGF-IR and IGF-IIR of RTK signaling showed a lower expression in mESCs, these molecules related to embryo development may be restrained in mESCs. The expression levels of the Delta and HESS in Notch signaling were enriched in mESCs. The expression of the molecules related to BMP and JAK-STAT signaling pathways were similar or at a slightly lower level in mESCs compared to those in MEF and NIH3T3 cells. It is suggested that the observed differences in gene expression profiles among the signaling pathways may contribute to the self-renewal and differentiation of mESCs in a signaling-specific manner.

Hormonal Analysis of Female Transgender Patients Performed Gender Reassignment Operation (여성 성전환수술을 받은 환자의 호르몬 정량분석)

  • Park, Jung Min;Kwon, Yong Seok;Lee, Keun Cheol;Kim, Seok Kwun;Kwak, Hyun;Kim, Sang Beom
    • Archives of Plastic Surgery
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    • v.32 no.6
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    • pp.699-705
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    • 2005
  • Transgender is the severe type of gender identity disorder. The prevalence rate of transgender is reported to occur to about 1 out of 50,000 men, and about 1 out of 10,000 women. As for Korea, it is estimated to have about 1400 transgender patients. Lately, not only the numbers of them are increasing but also they are influencing our society increasingly. As for female transgender patients, they take female hormone for a long term before and even after the operation to maintain their physical identity of female. We have analyzed insulin like growth factor-1(IGF-1), insulin like growth factor protein binding-3(IGFBP-3), female hormone, male hormone and thyroid hormone in female transgender patients who have undergone the gender reassignment operation. We examined the changes of hormone level due to having female hormone steadily, and also examined how the steady use of the hormone could affect body organs. As for IGF-1, it showed significantly low in the female transgender group compared to control ($319.30{\pm}37.4$ vs $539{\pm}55.0$, p<0.05). As for IGFBP-3, there was no significant difference ($2859{\pm}200.3$ vs $2607{\pm}262.5$, p>0.05). As for female hormone, there was no significant differences in FSH($13.42{\pm}13.8$ vs $8.95{\pm}3.5$, p>0.05), estradiol($104.41{\pm}97.1$ vs $121.68{\pm}60.2$, p>0.05), and LH($7.62{\pm}5.6$ vs $7.4{\pm}3.3$, p>0.05). Even in comparison of testosterone, there was no significant differences($0.23{\pm}0.09$ vs $0.33{\pm}1.33$, p>0.05). As for thyroid hormone, there was no significant differences in TSH and free T4($1.34{\pm}0.94$ vs $1.71{\pm}0.12$, $1.4{\pm}0.37$ vs $1.46{\pm}0.17$, p>0.05). Therefore, this study concludes that apart from the decreased level of IGF-1, the possible endocrine side-effect problem due to female hormone seems to be low because there was no differences of female, male, and thyroid hormone level compared with normal female. Further study will be required in metabolic change including bone metabolism occurred by decrease level of IGF-I.

Alterations of mRNA and lncRNA profiles associated with the extracellular matrix and spermatogenesis in goats

  • Chen, Haolin;Miao Xiaomeng;Xu, Jinge;Pu, Ling;Li, Liang;Han, Yong;Mao, Fengxian;Ma, Youji
    • Animal Bioscience
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    • v.35 no.4
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    • pp.544-555
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    • 2022
  • Objective: Spermatozoa are produced within the seminiferous tubules after sexual maturity. The expression levels of mRNAs and lncRNAs in testicular tissues are different at each stage of testicular development and are closely related to formation of the extracellular matrix (ECM) and spermatogenesis. Therefore, we set out to study the expression of lncRNAs and mRNAs during the different developmental stages of the goat testis. Methods: We constructed 12 RNA libraries using testicular tissues from goats aged 3, 6, and 12 months, and studied the functions of mRNAs and lncRNAs using the gene ontogeny (GO) and Kyoto encyclopedia of genes and genomes (KEGG) databases. Relationships between differentially expressed genes (DEGs) were analyzed by lncRNA-mRNA co-expression network and protein-protein interaction network (PPI). Finally, the protein expression levels of matrix metalloproteinase 2 (MMP2), insulin-like growth factor 2 (IGF2), and insulin-like growth factor-binding protein 6 (IGFBP6) were detected by western blotting. Results: We found 23, 8, and 135 differentially expressed lncRNAs and 161, 12, and 665 differentially expressed mRNAs that were identified between 3 vs 6, 6 vs 12, and 3 vs 12 months, respectively. GO, KEGG, and PPI analyses showed that the differential genes were mainly related to the ECM. Moreover, MMP2 was a hub gene and co-expressed with the lncRNA TCONS-0002139 and TCONS-00093342. The results of quantitative reverse-transcription polymerase chain reaction verification were consistent with those of RNA-seq sequencing. The expression trends of MMP2, IGF2, and IGFBP6 protein were the same as that of mRNA, which all decreased with age. IGF2 and MMP2 were significantly different in the 3 vs 6-month-old group (p<0.05). Conclusion: These results improve our understanding of the molecular mechanisms involved in sexual maturation of the goat testis.

Effects of Flavonoid from Rhus verniciflua on Testosterone Secretion by Rat Leydig Cells In Vitro (옻나무 유래 Flavonoid 처리가 흰쥐 Leydig 세포의 체외배양에서 Testosterone 분비에 미치는 영향)

  • 성환후;최선호;장유민;민관식;우제현;장원경;정남철;나천수;정일정
    • Korean Journal of Animal Reproduction
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    • v.25 no.2
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    • pp.125-130
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    • 2001
  • This study was performed to report a direct dose dependent stimulatory effect of the Flavonoid(F) on basal testosterone secretion and a dose dependent effect on LH induced testosterone production by Leydig cell of matured rats in vitro culture. F was obtained kom the Rhus vernicifua through aceton extraction and silica gel adsorption column chromatography. Leydig cells (1$\times$10$^{6}$ cells/well) from 12 weeks old rats were incubated with or without F(0, 20, 40, 80, 160 ng) or insulin-like growth factor-I(IGF-I) in the presence or absence of LH(10, 100ng). 1. The maximal stimulatory concentrations of testosterone in culture media were showed at 24hr of culture. but these testosterone level were decreased at 36 hr of culture. 2. Flavonoid(80ng) were significantly(P < 0.05) increased testosterone production compared with control groups for 12 hr culture. 3. Testosterone secretion by Leydig cells stimulated with LH(10, 100ng) for 6 hr and 12hr culture compared with 3 hr culture. 4. LH 10 ng augmented testosterone were increased by addition of F 40 ng for 12 hr culture. 5. F(0 and 40 ng) also enhanced LH 10 ng stimulated testosterone for 3 hr Leydig cells culture. 6. Addition of IGF-I 100 ng to the culture medium for 6 hr were increased the concentration of testosterone by Leydig cells stimulated with 100 ng LH. These results indicate that Flavonoid has a direct stimulatory effect on basal testosterone secretion in rat Leydig cells, and also modulates LH mediated testosterone. Therefore, Flavonoid may act as a modulator on gonadal development or gonadal steroidogenesis in direct or indirect.

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Correlations of cord blood Ghrelin and leptin concentrations with anthropometry of appropriate for gestational age newborns (적정체중아 제대혈의 ghrelin 및 leptin 농도와 신체계측치의 관계)

  • Lee, Jin;Moon, Se Na;Park, So Hyun;Jung, Min-Ho;Suh, Byung Kyu;Lee, Byung Churl
    • Clinical and Experimental Pediatrics
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    • v.49 no.1
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    • pp.93-98
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    • 2006
  • Purpose : Ghrelin stimulates the secretion of growth hormone and other pituitary hormones, and has orexigenic effects. It may have a physiologic role in fetal and neonatal growth. Leptin secreted by the adipocytes reflects fat mass in infants as well as adults. The aim of this study was to evaluate the relation of cord blood ghrelin and leptin levels to body weight(BW), body mass index(BMI), insulin-like growth factor-I(IGF-I) and insulin-like growth factor binding protein-3(IGFBP-3) levels in appropriate for gestational age(AGA) newborns. Methods : Sixty healthy AGA newborns(31 males and 29 females, gestational age[GA] 34-42 weeks) were included in this study, whose BW and BMI were measured at delivery. Umbilical cord venous blood samples were withdrawn, and ghrelin and leptin were measured by radioimmunoassay. Cord blood IGF-I and IGFBP-3 were determined by immunoradiometric assay. Results : The mean levels of ghrelin were inversely correlated with BW(r=-0.29, P<0.05) and GA (r=-0.28, P<0.05), but were not affected by gender. The mean levels of leptin levels showed positive correlation with BW(r=0.44, P<0.01), GA(r=0.36, P<0.01), and BMI(r=0.28, P<0.05). The leptin levels of females were higher than those of males. There was no gender difference in leptin levels in neonates under GA 37 weeks. However, the leptin levels of females were higher than those of males (P<0.01) in newborns with GA 37 weeks or over. There was no correlation between ghrelin and leptin levels. Ghrelin and leptin levels showed no relations to cord blood IGF-I and IGFBP-3 levels. Conclusion : These data suggest that cord blood ghrelin may have an inverse correlation with BW in AGA newborns, and leptin levels are positively correlated with BW and fat mass. Further study of ghrelin concentrations in cord blood is necessary to elucidate the physiological and pathological roles of ghrelin during the fetal and neonatal periods.