Inactivation of Max-interacting Protein 1 Induces Renal Cilia Disassembly through Reduction in Levels of Intraflagellar Transport 20 in Polycystic Kidney

Ko, Je Yeong,Yoo, Kyung Hyun,Song, Seon Ah,Kim, Do Yeon,Kong, Hyun Kyung,Ahn, Curie,Lee, Han Woong,Kang, Duk-Hee,Oh, Goo Taeg,Park, Jong Hoon American Society for Biochemistry and Molecular Bi 2013 JOURNAL OF BIOLOGICAL CHEMISTRY - Vol.288 No.9

<P>Cilia in ciliated cells consist of protruding structures that sense mechanical and chemical signals from the extracellular environment. Cilia are assembled with variety molecules via a process known as intraflagellar transport (IFT). What controls the length of cilia in ciliated cells is critical to understand ciliary disease such as autosomal dominant polycystic kidney disease, which involves abnormally short cilia. But this control mechanism is not well understood. Previously, multiple tubular cysts have been observed in the kidneys of max-interacting protein 1 (<I>Mxi1</I>)-deficient mice aged 6 months or more. Here, we clarified the relationship between Mxi1 inactivation and cilia disassembly. Cilia phenotypes were observed in kidneys of <I>Mxi1</I>-deficient mice using scanning electron microscopy to elucidate the effect of Mxi1 on renal cilia phenotype, and cilia disassembly was observed in <I>Mxi1</I>-deficient kidney. In addition, genes related to cilia were validated <I>in vitro</I> and <I>in vivo</I> using quantitative PCR, and <I>Ift20</I> was selected as a candidate gene in this study. The length of cilium decreased, and <I>p</I>-ERK level induced by a cilia defect increased in kidneys of <I>Mxi1</I>-deficient mice. Ciliogenesis of <I>Mxi1</I>-deficient mouse embryonic fibroblasts (MEFs) decreased, and this abnormality was restored by <I>Mxi1</I> transfection in <I>Mxi1</I>-deficient MEFs. We confirmed that ciliogenesis and <I>Ift20</I> expression were regulated by Mxi1 <I>in vitro</I>. We also determined that Mxi1 regulates <I>Ift20</I> promoter activity via Ets-1 binding to the <I>Ift20</I> promoter. These results indicate that inactivating Mxi1 induces ciliary defects in polycystic kidney.</P>

Interplay Between Primary Cilia and Autophagy and Its Controversial Roles in Cancer

( Je Yeong Ko ),( Eun Ji Lee ),( Jong Hoon Park ) 한국응용약물학회 2019 Biomolecules & Therapeutics(구 응용약물학회지) Vol.27 No.4

Primary cilia and autophagy are two distinct nutrient-sensing machineries required for maintaining intracellular energy homeostasis, either via signal transduction or recycling of macromolecules from cargo breakdown, respectively. Potential correlations between primary cilia and autophagy have been recently suggested and their relationship may increase our understanding of the pathogenesis of human diseases, including ciliopathies and cancer. In this review, we cover the current issues concerning the bidirectional interaction between primary cilia and autophagy and discuss its role in cancer with cilia defect.

Functional Enhancers As Master Regulators of Tissue-Specific Gene Regulation and Cancer Development

Ko, Je Yeong,Oh, Sumin,Yoo, Kyung Hyun Korean Society for Molecular and Cellular Biology 2017 Molecules and cells Vol.40 No.3

Tissue-specific transcription is critical for normal development, and abnormalities causing undesirable gene expression may lead to diseases such as cancer. Such highly organized transcription is controlled by enhancers with specific DNA sequences recognized by transcription factors. Enhancers are associated with chromatin modifications that are distinct epigenetic features in a tissue-specific manner. Recently, super-enhancers comprising enhancer clusters co-occupied by lineage-specific factors have been identified in diverse cell types such as adipocytes, hair follicle stem cells, and mammary epithelial cells. In addition, noncoding RNAs, named eRNAs, are synthesized at super-enhancer regions before their target genes are transcribed. Many functional studies revealed that super-enhancers and eRNAs are essential for the regulation of tissue-specific gene expression. In this review, we summarize recent findings concerning enhancer function in tissue-specific gene regulation and cancer development.

Invited Mini Review : Mouse models of polycystic kidney disease induced by defects of ciliary proteins

( Je Yeong Ko ),( Jong Hoon Park ) 생화학분자생물학회(구 한국생화학분자생물학회) 2013 BMB Reports Vol.46 No.2

Polycystic kidney disease (PKD) is a common hereditary disorder which is characterized by fluid-filled cysts in the kidney. Mutation in either PKD1, encoding polycystin-1 (PC1), or PKD2, encoding polycystin-2 (PC2), are causative genes of PKD. Recent studies indicate that renal cilia, known as mechanosensors, detecting flow stimulation through renal tubules, have a critical function in maintaining homeostasis of renal epithelial cells. Because most proteins related to PKD are localized to renal cilia or have a function in ciliogenesis. PC1/PC2 heterodimer is localized to the cilia, playing a role in calcium channels. Also, disruptions of ciliary proteins, except for PC1 and PC2, could be involved in the induction of polycystic kidney disease. Based on these findings, various PKD mice models were produced to understand the roles of primary cilia defects in renal cyst formation. In this review, we will describe the general role of cilia in renal epithelial cells, and the relationship between ciliary defects and PKD. We also discuss mouse models of PKD related to ciliary defects based on recent studies. [BMB Reports 2013; 46(2): 73-79].

Matrix metalloproteinase-13 downregulation and potential cartilage protective action of the Korean Red Ginseng preparation

Je Hyeong Lee,Omer Shehzad,Sung Kwon Ko,Yeong Shik Kim,Hyun Pyo Kim 고려인삼학회 2015 Journal of Ginseng Research Vol.39 No.3

Background: The present study was designed to prepare and find the optimum active preparation or fraction from Korea Red Ginseng inhibiting matrix metalloproteinase-13 (MMP-13) expression, because MMP-13 is a pivotal enzyme to degrade the collagen matrix of the joint cartilage. Methods: From total red ginseng ethanol extract, n-BuOH fraction (total ginsenoside-enriched fraction), ginsenoside diol-type-enriched fraction (GDF), and ginsenoside triol-type-enriched fraction (GTF) were prepared, and ginsenoside diol type-/F4-enriched fraction (GDF/F4) was obtained from Panax ginseng leaf extract. Results: The n-BuOH fraction, GDF, and GDF/F4 clearly inhibited MMP-13 expression compared to interleukin-1b-treated SW1353 cells (human chondrosarcoma), whereas the total extract and ginsenoside diol-type-enriched fraction did not. In particular, GDF/F4, the most effective inhibitor, blocked the activation of p38 mitogen-activated protein kinase (p38 MAPK), c-Jun-activated protein kinase (JNK), and signal transducer and activator of transcription-1/2 (STAT-1/2) among the signal transcription pathways involved. Further, GDF/F4 also inhibited the glycosaminoglycan release from interleukin-1a-treated rabbit cartilage culture (30.6% inhibition at 30 μg/mL). Conclusion: Some preparations from Korean Red Ginseng and ginseng leaves, particularly GDF/F4, may possess the protective activity against cartilage degradation in joint disorders, and may have potential as new therapeutic agents.

Matrix metalloproteinase-13 downregulation and potential cartilage protective action of the Korean Red Ginseng preparation

Lee, Je Hyeong,Shehzad, Omer,Ko, Sung Kwon,Kim, Yeong Shik,Kim, Hyun Pyo The Korean Society of Ginseng 2015 Journal of Ginseng Research Vol.39 No.1

Background: The present study was designed to prepare and find the optimum active preparation or fraction from Korea Red Ginseng inhibiting matrix metalloproteinase-13 (MMP-13) expression, because MMP-13 is a pivotal enzyme to degrade the collagen matrix of the joint cartilage. Methods: From total red ginseng ethanol extract, n-BuOH fraction (total ginsenoside-enriched fraction), ginsenoside diol-type-enriched fraction (GDF), and ginsenoside triol-type-enriched fraction (GTF) were prepared, and ginsenoside diol type-/F4-enriched fraction (GDF/F4) was obtained from Panax ginseng leaf extract. Results: The n-BuOH fraction, GDF, and GDF/F4 clearly inhibited MMP-13 expression compared to interleukin-$1{\beta}$-treated SW1353 cells (human chondrosarcoma), whereas the total extract and ginsenoside diol-type-enriched fraction did not. In particular, GDF/F4, the most effective inhibitor, blocked the activation of p38 mitogen-activated protein kinase (p38 MAPK), c-Jun-activated protein kinase (JNK), and signal transducer and activator of transcription-1/2 (STAT-1/2) among the signal transcription pathways involved. Further, GDF/F4 also inhibited the glycosaminoglycan release from interleukin-$1{\alpha}$-treated rabbit cartilage culture (30.6% inhibition at $30{\mu}g/mL$). Conclusion: Some preparations from Korean Red Ginseng and ginseng leaves, particularly GDF/F4, may possess the protective activity against cartilage degradation in joint disorders, and may have potential as new therapeutic agents.

항공엔진 시동기어박스 검증용 시험리그 개발

김선제(Sun Je Kim),김광민(Gwang Min Kim),고준영(Jun Young Ko),김용련(Yeong-Ryeon Kim) 한국추진공학회 2019 한국추진공학회 학술대회논문집 Vol.2019 No.5

전기차 사용 후 배터리 잔존가치 평가방법 개선 시험 연구

강일영(Il-Yeong Kang),김형진(Hyeong-Jin Kim),고용제(Yong-Je Ko),박형민(Hyung-Min Park),고현주(Hyun-Ju Ko),장소현(So-Hyun Jang),홍정현(Jung-Hyun Hong) 대한전기학회 2022 대한전기학회 학술대회 논문집 Vol.2022 No.7

전기차 사용 후 배터리 산업 활성화를 위해 배터리 잔존가치평가 시간 단축 등 평가 방법의 개선이 필요하다. 완전충방전을 주로 하는 용량시험의 실측 데이터를 중심으로 잔존가치평가 측정방법 개선을 위한 연구를 수행하였다. 배터리 용량 10% 부분방전 시험 결과 완전충방전 시험과의 오차율이2% 내로 산출되어 활용 가능함을 확인하였다. 배터리 검사 공정 소요 시간의 기존 대비 약 70%의 단축 효과를 보였다. 전기차 사용 후 배터리 잔존가치 평가 공정시간 단축으로 재사용 배터리 산업 경쟁력 확보에 도움이 될 것으로 기대된다.

Long non-coding RNAs: key regulators of liver and kidney fibrogenesis

( Su-hyang Han ),( Je Yeong Ko ),( Eun Seo Kang ),( Jong Hoon Park ),( Kyung Hyun Yoo ) 생화학분자생물학회 2023 BMB Reports Vol.56 No.7

Fibrosis is a pathological condition that is characterized by an abnormal buildup of extracellular matrix (ECM) components, such as collagen, in tissues. This condition affects various organs of the body, including the liver and kidney. Early diagnosis and treatment of fibrosis are crucial, as it is a progressive and irreversible process in both organs. While there are certain similarities in the fibrosis process between the liver and kidney, there are also significant differences that must be identified to determine molecular diagnostic markers and potential therapeutic targets. Long non-coding RNAs (lncRNAs), a class of RNA molecules that do not code for proteins, are increasingly recognized as playing significant roles in gene expression regulation. Emerging evidence suggests that specific lncRNAs are involved in fibrosis development and progression by modulating signaling pathways, such as the TGF-β/Smad pathway and the β-catenin pathway. Thus, identifying the precise lncRNAs involved in fibrosis could lead to novel therapeutic approaches for fibrotic diseases. In this review, we summarize lncRNAs related to fibrosis in the liver and kidney, and propose their potential as therapeutic targets based on their functions. [BMB Reports 2023; 56(7): 374-384]

IFT46 plays an essential role in cilia development

Lee, Mi-Sun,Hwang, Kyu-Seok,Oh, Hyun-Woo,Ji-Ae, Kim,Kim, Hyun-Taek,Cho, Hyun-Soo,Lee, Jeong-Ju,Yeong Ko, Je,Choi, Jung-Hwa,Jeong, Yun-Mi,You, Kwan-Hee,Kim, Joon,Park, Doo-Sang,Nam, Ki-Hoan,Aizawa, Shi Elsevier 2015 Developmental Biology Vol.400 No.2

<P><B>Abstract</B></P> <P>Cilia are microtubule-based structures that project into the extracellular space. Ciliary defects are associated with several human diseases, including polycystic kidney disease, primary ciliary dyskinesia, left–right axis patterning, hydrocephalus and retinal degeneration. However, the genetic and cellular biological control of ciliogenesis remains poorly understood. The IFT46 is one of the highly conserved intraflagellar transport complex B proteins. In zebrafish, <I>ift46</I> is expressed in various ciliated tissues such as Kupffer׳s vesicle, pronephric ducts, ears and spinal cord. We show that <I>ift46</I> is localized to the basal body. Knockdown of <I>ift46</I> gene results in multiple phenotypes associated with various ciliopathies including kidney cysts, pericardial edema and ventral axis curvature. In <I>ift46</I> morphants, cilia in kidney and spinal canal are shortened and abnormal. Similar ciliary defects are observed in otic vesicles, lateral line hair cells, olfactory pits, but not in Kupffer׳s vesicle. To explore the functions of <I>Ift46</I> during mouse development, we have generated <I>Ift46</I> knock-out mice. The <I>Ift46</I> mutants have developmental defects in brain, neural tube and heart. In particular <I>Ift46</I>(−/−) homozygotes displays randomization of the embryo heart looping, which is a hallmark of defective left–right (L/R) axis patterning. Taken together, our results demonstrated that IFT46 has an essential role in vertebrate ciliary development.</P> <P><B>Highlights</B></P> <P> <UL> <LI> IFT46 over-expression induces apoptosis in developing zebrafish embryos. </LI> <LI> Loss of IFT46 displays typical phenotypes of ciliary defects in zebrafish and mice. </LI> <LI> IFT46 C-terminal domain is required for IFT46 function. </LI> <LI> IFT46 is not essential for axonemal dynein assembly in zebrafish. </LI> </UL> </P>