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Jane Jung,모정순,김미연,안은정,Ji-Hye Yoon,박희세 한국분자세포생물학회 2011 Molecules and cells Vol.32 No.2
Notch signaling involves the proteolytic cleavage of the transmembrane Notch receptor after binding to its trans-membrane ligands. The Delta-like ligand 1 also undergoes proteolytic cleavage upon Notch binding, resulting in the production of a free intracellular domain. In this study, we have demonstrated that the Delta-like 1 intracellular domain (Dll1-IC) specifically binds to Notch1-IC in the nucleus, thereby disrupting the association of the Notch1-IC-RBP-Jk-MAM transcription activator complex. Additionally, the Notch1-mediated blockage of the induction of MyoD is abolished by the co-expression of Dll1-IC. Collectively, our results show that Dll1-IC functions as a negative regulator in Notch signaling via the disruption of the Notch1-IC-RBP-Jk complex.
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유방암세포에서 LATS1/2 활성에 의한 당귀 추출물의 항암효과
김초롱,김남빈,정한솔,신유수,모정순 한의병리학회 2020 동의생리병리학회지 Vol.34 No.4
The Hippo-YAP signaling pathway is critical for cell proliferation, survival, and self-renewal in both Drosophila and mammals. Disorder of Hippo-YAP pathway leads to tumor development, progression and poor prognosis in various cancers. YAP/TAZ are the key downstream effectors of the Hippo pathway and they can be inhibited through LATS1/2, core kinases in the Hippo pathway, mediated phosphorylation. In this study, we investigated the effect of Angelica gigas Nakai extract (AGNE) on Hippo-YAP/TAZ pathway. First, ANGE induced YAP/TAZ phosphorylation and dissociation of the YAP/TAZ-TEAD transcription complex. By qRT-PCR, we found that ANGE inhibits the expression of YAP/TAZ-TEAD target gene, CTGF and CYR61. In addition, the transcriptional activity of YAP/TAZ was not suppressed significantly in LATS1/2 double-knockout (DKO) cells by ANGE compared to LATS1/2 wild-type (WT) cells, which means AGNE inhibits YAP/TAZ signaling through direct action on LATS1/2. Further, it was confirmed that AGNE-induced activation of LATS1/2 inhibited the migration potential of the vector-expressing cells by suppressing YAP/TAZ activity. The reduced migration potential was restored in active YAP-TEAD expressing cells. Taken together, the results of this study indicate that ANGE downregulates YAP/TAZ signaling in cells through the activation of LATS1/2.
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강하람,임수빈,김초롱,모정순,박수정,정한솔 한의병리학회 2023 동의생리병리학회지 Vol.37 No.4
Renal fibrosis (RF) is a prominent pathological feature of chronic kidney disease (CKD), characterized by excessive accumulation of extracellular matrix components, resulting in progressive renal function loss. The fibroblast-to-myofibroblast transition (FMT) plays a pivotal role in renal fibrosis pathogenesis, driving aberrant deposition of extracellular matrix proteins and disruption of tissue architecture. Targeting FMT has emerged as a promising strategy to combat renal fibrosis and preserve kidney function. Silymarin, a flavonoid extract derived from Silybum marianum seeds, has gained attention for its therapeutic potential, particularly in liver diseases, due to its potent antioxidant and anti-inflammatory properties. However, the precise mechanisms underlying its effects on FMT remain unclear. This study aimed to investigate the therapeutic potential of silymarin in inhibiting FMT in NRK-49F renal interstitial fibroblasts. Transforming growth factor-beta 1(TGF-β1) plays a crucial role in promoting FMT through the activation of intracellular signaling pathways and induction of key fibrotic markers, including alpha-smooth muscle actin (α-SMA) and vimentin. Silymarin demonstrated significant downregulation of FMT markers, including α-SMA and vimentin, in TGF-β1-stimulated NRK-49F cells. Our findings highlight silymarin as a promising therapeutic candidate for mitigating renal fibrosis and managing CKD.
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