• Asian-Australasian Journal of Animal Sciences
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• 제23권3호
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• pp.326-332
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• 2010

Daidzein, a natural isoflavonoid phytoestrogen, structurally resembles estradiol (E2) and possesses estrogenic activity. This study was designed to test the hypothesis that daidzein may mimic the effects of E2 on ovine follicle development by regulation of the mRNA expression of bone morphogenetic protein receptor genes and thereby influence the reproductive system. Granulosa cells were cultured in serum-free McCoy's 5A medium with and without supplementation of daidzein. Results showed that daidzein (10-100 ng/ml) significantly increased the proliferation of ovine granulosa cells (p<0.05), but inhibited the growth of granulosa cells at a dose of 1,000 ng/ml (p<0.01). Daidzein inhibited progesterone production in a dose dependent manner; however, it did not affect estradiol production by granulosa cells. We also investigated the effects of daidzein on BMPRII, BMPRIB and ALK-5 mRNA expression in ovine granulosa cells by quantitative real-time PCR. Treatment of granulosa cells with daidzein increased significantly expression of these genes at 10-100 ng/ml. Thus, these data suggested that a low concentration of daidzein (10-100 ng/ml) had a direct stimulatory effect on ovine granulosa cells while a high concentration was toxic.

• Clinical and Experimental Reproductive Medicine
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• 제48권3호
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• pp.245-254
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• 2021

Objective: In humans, polycystic ovary syndrome (PCOS) is an androgen-dependent ovarian disorder. Aberrant gene expression in folliculogenesis can arrest the transition of preantral to antral follicles, leading to PCOS. We explored the possible role of altered gene expression in preantral follicles of estradiol valerate (EV) induced polycystic ovaries (PCO) in a mouse model. Methods: Twenty female balb/c mice (8 weeks, 20.0±1.5 g) were grouped into control and PCO groups. PCO was induced by intramuscular EV injection. After 8 weeks, the animals were killed by cervical dislocation. Blood serum (for hormonal assessments using the enzyme-linked immunosorbent assay technique) was aspirated, and ovaries (the right ovary for histological examinations and the left for quantitative real-time polymerase) were dissected. Results: Compared to the control group, the PCO group showed significantly lower values for the mean body weight, number of preantral and antral follicles, serum levels of estradiol, luteinizing hormone, testosterone, and follicle-stimulating hormone, and gene expression of TGFB1, GDF9 and BMPR2 (p<0.05). Serum progesterone levels were significantly higher in the PCO animals than in the control group (p<0.05). No significant between-group differences (p>0.05) were found in BMP6 or BMP15 expression. Conclusion: In animals with EV-induced PCO, the preantral follicles did not develop into antral follicles. In this mouse model, the gene expression of TGFB1, GDF9, and BMPR2 was lower in preantral follicles, which is probably related to the pathologic conditions of PCO. Hypoandrogenism was also detected in this EV-induced murine PCO model.

• Molecules and Cells
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• 제39권5호
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• pp.389-394
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• 2016

Dovitinib (TKI258) is a small molecule multi-kinase inhibitor currently in clinical phase I/II/III development for the treatment of various types of cancers. This drug has a safe and effective pharmacokinetic/pharmacodynamic profile. Although dovitinib can bind several kinases at nanomolar concentrations, there are no reports relating to osteoporosis or osteoblast differentiation. Herein, we investigated the effect of dovitinib on human recombinant bone morphogenetic protein (BMP)-2-induced osteoblast differentiation in a cell culture model. Dovitinib enhanced the BMP-2-induced alkaline phosphatase (ALP) induction, which is a representative marker of osteoblast differentiation. Dovitinib also stimulated the translocation of phosphorylated Smad1/5/8 into the nucleus and phosphorylation of mitogen-activated protein kinases, including ERK1/2 and p38. In addition, the mRNA expression of BMP-4, BMP-7, ALP, and OCN increased with dovitinib treatment. Our results suggest that dovitinib has a potent stimulating effect on BMP-2-induced osteoblast differentiation and this existing drug has potential for repositioning in the treatment of bone-related disorders.

• Journal of Chest Surgery
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• 제36권2호
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• pp.86-90
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• 2003

폐 형성에 활성적인 또는 억제적인 기능을 갖고 있다고 알려져 있는 FGF-7 성장인자, BMP수용체 II, 그리고 TGF-$\beta$ 수용체 II 유전자의 비정상 발현이 폐기포 생성에 관여하는지를 각각의 단일성 클론 항체를 사용하여 수술로 절제된 자연기흉 환자의 폐기포 조직들을 면역조직염색 방법으로 염색하여 관찰하였다. 대상 및 방법: 재발성 또는 지속성 기흉으로 흉강경 또는 개흉술로 폐기포 절제술을 실시한 환자들을 대상으로 하였다. 총 31명의 환자로 15세에서 39세까지 연령분포를 보였으며 남자 30명, 여자 1명이었다. 폐기포 절제는 비디오흉강경이나 소절개개흠술을 통하여 폐기포벽에 손상을 가하지 않게 주의하면서 비디오흉강경용 스태플러(Endo GIA stapler)를 이용하여 절제하였으며 가능한 원형을 유지하여 신선한 상태로 포르마린에 고정하여 면역조직화학적 연구를 위한 표본을 만들었다. 폐기포 조직 슬라이드를 단일클론성 항 TGF-$\beta$ 수용체 II, BMP수용체 II 그리고 FGF-7인자 항체를 이용하여 면역조직학적 염색방법으로 관찰하였다. 결과: 전체 환자 31명중 TGF-$\beta$ 수용체 II항체에 양성 반응을 나타낸 환자수는 모두 24명이었다. 이들 중에는 18명이 강한 양성 반응을 보였고, 6명이 약한 양성 반응을 보였다 면역조직화학적 염색 결과를 고배율 현미경으로 살펴보면, TGF-$\beta$ 수용체 II의 염색이 기흉과 정상 폐조직 경계 부위에서 측히 강하게 염색됨이 관찰되었다. 이에 반하여, BMP수용체 II 그리고 FGF-7인자의 항체를 이용한 면역조직학적 염색 결과는 모든 환자의 조직들에서 음성으로 관찰되었다. 결론: 폐 조직이 형성될 때, 억제유전자의 역할을 담당하고 있다고 알려진 TGF-$\beta$ 수용체 II의 발현이 증가되면서 폐기포가 생성될 수 있다는 가능성을 제시하였다. 이번 결론은 면역조직학적 염색 실험 결과만으로 밝혀진 사실임으로 좀 더 체계적인 분자생물학적 인 연구가 요구된다.