• Journal of Ginseng Research
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• 제37권3호
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• pp.261-268
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• 2013

The ginseng plant (Panax ginseng Meyer) has a large number of active ingredients including steroidal saponins with a dammarane skeleton as well as protopanaxadiol and protopanaxatriol, commonly known as ginsenosides, which have antioxidant, anticancer, antidiabetic, anti-adipocyte, and sexual enhancing effects. Though several discoveries have demonstrated that ginseng saponins (ginsenosides) as the most important therapeutic agent for the treatment of osteoporosis, yet the molecular mechanism of its active metabolites is unknown. In this review, we summarize the evidence supporting the therapeutic properties of ginsenosides both in vivo and in vitro, with an emphasis on the different molecular agents comprising receptor activator of nuclear factor kappa-B ligand, receptor activator of nuclear factor kappa-B, and matrix metallopeptidase-9, as well as the bone morphogenetic protein-2 and Smad signaling pathways.

• BMB Reports
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• 제50권2호
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• pp.58-59
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• 2017

The beneficial paracrine roles of mesenchymal stem cells (MSCs) in tissue repair have potential in therapeutic strategies against various diseases. However, the key therapeutic factors secreted from MSCs and their exact molecular mechanisms of action remain unclear. In this study, the cell-free secretome of umbilical cord-derived MSCs showed significant anti-fibrotic activity in the mouse models of liver fibrosis. The involved action mechanism was the regulation of hepatic stellate cell activation by direct inhibition of the $TGF{\beta}$/Smad-signaling. Antagonizing the milk fat globule-EGF factor 8 (MFGE8) activity blocked the anti-fibrotic effects of the MSC secretome in vitro and in vivo. Moreover, MFGE8 was secreted by MSCs from the umbilical cord as well as other tissues, including teeth and bone marrow. Administration of recombinant MFGE8 protein alone had a significant anti-fibrotic effect in two different models of liver fibrosis. Additionally, MFGE8 downregulated $TGF{\beta}$ type I receptor expression by binding to ${\alpha}v{\beta}3$ integrin on HSCs. These findings revealed the potential role of MFGE8 in modulating $TGF{\beta}$-signaling. Thus, MFGE8 could serve as a novel therapeutic agent for liver fibrosis.

• 대한한의학회지
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• 제27권3호
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• pp.26-37
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• 2006

Determination and differentiation of cells in the skeletal muscle lineage is positively regulated by cell-cell contact. Differentiation proteins proposed to mediate this effect include both classical MyoD and MEF members; potential interactions between the promyogenic activities of these classes of protein, however, are unknown. We show here that MyoD and MEF, two promyogenic family members that relate to each other in a cis fashion, form interactions with MyoD and MEF. These proteins contain myosin-heavy chainsand are enriched at sites of cell-cell contact between myoblasts. Therefore, in differentiation of MyoD and MEF from Chungsimyeonjaeum interact dependently, suggesting that the interactions occur in a cis fashion; consistent with this conclusion, MyoD-mediated differentiation is required for myoblasts to occur by Chungsimyeonjaeum. Inhibition in myoblasts of a MyoD by Staurosporine in its ability to associate with MEF interferes with differentiation as assessed by morphological and transcription levels, suggesting that this interaction is functionally important in myogenesis. Also, some of the differentiation-mediated proteins that are required for myogenesis seem to be based on interdependent activities of the promyogenic classical smad-subfamily.

• Molecules and Cells
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• 제22권3호
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• pp.291-299
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• 2006

Vitexin, a natural flavonoid compound identified as apigenin-8-C-${\beta}$-D-glucopyranoside, has been reported to exhibit antioxidative and anti-inflammatory properties. In this study, we investigated its effect on hypoxiainducible factor-$1{\alpha}$ (HIF-$1{\alpha}$) in rat pheochromacytoma (PC12), human osteosarcoma (HOS) and human hepatoma (HepG2) cells. Vitexin inhibited HIF-$1{\alpha}$ in PC12 cells, but not in HOS or HepG2 cells. In addition, it diminished the mRNA levels of hypoxia-inducible genes such as vascular endothelial growth factor (VEGF), smad3, aldolase A, enolase 1, and collagen type III in the PC12 cells. We found that vitexin inhibited the migration of PC12 cells as well as their invasion rates, and it also inhibited tube formation by human umbilical vein endothelium cells (HUVECs). Interestingly, vitexin inhibited the hypoxia-induced activation of c-jun N-terminal kinase (JNK), but not of extracellular-signal regulated protein kinase (ERK), implying that it acts in part via the JNK pathway. Overall, these results suggest the potential use of vitexin as a treatment for diseases such as cancer.

• Biomolecules & Therapeutics
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• 제25권4호
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• pp.417-426
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• 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.

• Journal of Periodontal and Implant Science
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• 제36권3호
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• pp.627-637
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• 2006

이 연구는 rh BMP-7-immobilized substrates에 대한 백서 태자 두개관 세포의 반응을 석회화 결절 측정, 알카리 효소 분석, 역전사 중합반응 및 단백질 분석등으로 평가하여 다음과 같은 결과를 얻었다. 1. 배양 14일 째, 석회화 결절 형성율을 측정한 결과, rh BMP-7-immobilized substrates에서 대조군과 비교하여 더 많은 석회화 결절을 형성하였다. 2. 배양 7일에 염기성 인산 분해효소 활성도는 rh BMP-7-immobilized substrates에서 대조군에 비해 효소 활성도가 유의하게 높았다. 3. 역전사 중합반응의 결과에서 BSP 와 OCN 유전자 발현은 대조군보다 더 현저하였다. 4. 단백질 분석에서 rh BMP-7-immobilized substrates와 대조군 모두 Smad 1,5,8 단백질의 인산화를 활성화시키지 못했다. 이상의 결과 rh BMP-7-immobilized substrates는 백서 태자 두개관세포가 조골세포로의 분화와 석회화를 유도하며 따라서 rh BMP-7-immobilized substrates는 임프란트 주변의 골 형성에 유용하리라 사료된다.

• BMB Reports
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• 제57권3호
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• pp.143-148
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• 2024

Pulmonary fibrosis is a serious lung disease that occurs predominantly in men. Genistein is an important natural soybean-derived phytoestrogen that affects various biological functions, such as cell migration and fibrosis. However, the antifibrotic effects of genistein on pulmonary fibrosis are largely unknown. The antifibrotic effects of genistein were evaluated using in vitro and in vivo models of lung fibrosis. Proteomic data were analyzed using nano-LC-ESI-MS/MS. Genistein significantly reduced transforming growth factor (TGF)-β1-induced expression of collagen type I and α-smooth muscle actin (SMA) in MRC-5 cells and primary fibroblasts from patients with idiopathic pulmonary fibrosis (IPF). Genistein also reduced TGF-β1-induced expression of p-Smad2/3 and p-p38 MAPK in fibroblast models. Comprehensive protein analysis confirmed that genistein exerted an anti-fibrotic effect by regulating various molecular mechanisms, such as unfolded protein response, epithelial mesenchymal transition (EMT), mammalian target of rapamycin complex 1 (mTORC1) signaling, cell death, and several metabolic pathways. Genistein was also found to decrease hydroxyproline levels in the lungs of BLM-treated mice. Genistein exerted an anti-fibrotic effect by preventing fibroblast activation, suggesting that genistein could be developed as a pharmacological agent for the prevention and treatment of pulmonary fibrosis.

• BMB Reports
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• 제39권6호
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• pp.686-695
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• 2006

Interleukin-2 enhancer binding factor 2 (ILF2) was reported to regulate transcription of interleukin-2 (IL-2), a central cytokine in the regulation of T-cell responses. This property of ILF2 was well characterized in human and mammals, but little is known in bony fish. In this paper, an ILF2 homologue was cloned and well characterized from Tetraodon nigrovirid is for the further investigation of the function of ILF2 in bony fish. The full-length Tetraodon ILF2 cDNA was 1380 bp in size and contained an open reading frame (ORF) of 1164 bp that translates into a 387 amino-acid peptide with a molecular weight of 42.9 kDa, a 5' untranslated region (UTR) of 57 bp, and a 3' UTR of 159 bp containing a poly A tail. The deduced peptide of Tetraodon ILF2 shared an overall identity of 58%~93% with other known ILF2 sequences, and contained two N-glycosylation sites, two N-myristoylation sites, one RGD cell attachment sequence, six protein kinase C phosphorylation sites, one amino-terminal RGG-rich single-stranded RNA-binding domain, and a DZF zinc-finger nucleic acid binding domain, most of which were highly conserved through species compared. Constitutive expression of Tetraodon ILF2 was observed in all tissues examined, including gill, gut, head kidney, spleen, liver, brain and heart. The highest expression was detected in heart, followed by liver, head kidney and brain. Stimulation with LPS did not significantly alter the expression of Tetraodon ILF2. Gene organization analysis showed that the Tetraodon ILF2 gene have fifteen exons, one more than other known ILF2 genes in human and mouse. Genes up- and down-stream from the Tetraodon ILF2 were Rpa12, Peroxin-11b, Smad4, Snapap and Txnip homologue, which were different from that in human and mouse.

• BMB Reports
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• 제50권6호
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• pp.308-317
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• 2017

Bone morphogenetic protein type 2 receptor (BMPR2) is one of the transforming growth $factor-{\beta}$ ($TGF-{\beta}$) superfamily receptors, performing diverse roles during embryonic development, vasculogenesis, and osteogenesis. Human BMPR2 consists of 1,038 amino acids, and contains functionally conserved extracellular, transmembrane, kinase, and C-terminal cytoplasmic domains. Bone morphogenetic proteins (BMPs) engage the tetrameric complex, composed of BMPR2 and its corresponding type 1 receptors, which initiates SMAD proteins-mediated signal transduction leading to the expression of target genes implicated in the development or differentiation of the embryo, organs and bones. In particular, genetic alterations of BMPR2 gene are associated with several clinical disorders, including representative pulmonary arterial hypertension, cancers, and metabolic diseases, thus demonstrating the physiological importance of BMPR2. In this mini review, we summarize recent findings regarding the molecular basis of BMPR2 functions in BMP signaling, and the versatile roles of BMPR2. In addition, various aspects of experimentally validated pathogenic mutations of BMPR2 and the linked human diseases will also be discussed, which are important in clinical settings for diagnostics and treatment.

• Molecules and Cells
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• 제45권5호
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• pp.329-342
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• 2022

The liver is the predominant metastatic site for pancreatic cancer. However, the factors that determine the liver metastasis and the specific molecular mechanisms are still unclear. In this study, we used human pancreatic cancer cell line Hs766T to establish Hs766T-L3, a subline of Hs766T with stable liver metastatic ability. We performed RNA sequencing of Hs766T-L3 and its parental cell line Hs766T, and revealed huge differences in gene expression patterns and pathway activation between these two cell lines. We correlated the difference in pathway activation with the expression of the four core transcriptional factors including STAT1, NR2F2, GATA2, and SMAD4. Using the TCGA database, we examined the relative expression of these transcription factors (TFs) in pan-cancer and their relationship with the prognosis of the pancreatic cancer. Among these TFs, we considered GATA2 is closely involved in tumor metastasis and may serve as a potential metastatic driver. Further in vitro and in vivo experiments confirmed that GATA2-mediated transcriptional activation of Notch3 promotes the liver metastasis of Hs766T-L3, and knockdown of either GATA2 or Notch3 reduces the metastatic ability of Hs766T-L3. Therefore, we claim that GATA2 may serve as a metastatic driver of pancreatic cancer and a potential therapeutic target to treat liver metastasis of pancreatic cancer.