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Gluconeogenic signals regulate hepcidin gene expression via a CRBN-KLF15 axis
( Jeong-rang Jo ),( Sung-eun Lee ),( Seungwon An ),( Balachandar Nedumaran ),( Swati Ghosh ),( Keun-gyu Park ),( Yong Deuk Kim ) 생화학분자생물학회(구 한국생화학분자생물학회) 2021 BMB Reports Vol.54 No.4
Hepcidin (HAMP) is synthesized in the liver. It is a key ironregulatory hormone that controls systemic iron homeostasis. Cereblon (CRBN) and Kruppel-like factor 15 (KLF15) are known to regulate diverse physiological functions. In this study, we investigated the role of CRBN on hepatic hepcidin gene expression and production under gluconeogenic stimuli. Fasted mice as well as forskolin (FSK)- and glucagon (GLU)-treated mice had reduced serum iron levels but increased expression levels of hepatic Crbn and Klf15 and hepcidin secretion. MicroRNA (miRNA) expression analysis of fasted and Ad-Crbninfected mice revealed significant reduction of microRNA-639 (miR-639). Hepatic overexpression of Crbn elevated hepcidin expression and production along with Klf15 gene expression, whereas knockdown of Crbn and Klf15 markedly decreased FSK- and fasting-mediated induction of hepcidin gene expression and its biosynthesis in mouse livers and primary hepatocytes. Moreover, expression of KLF15 significantly increased the activity of hepcidin reporter gene. It was exclusively dependent on the KLF15-binding site identified within the hepcidin gene promoter. Overall, this study demonstrates that CRBN and KLF15 are novel mediators of gluconeogenic signal-induced hepcidin gene expression and production. Thus, CRBN and KLF15 might be novel potential therapeutic targets to intervene metabolic dysfunction. [BMB Reports 2021; 54(4): 221-226]
Park, Hyun Woong,Kang, Min Gyu,Kim, Kyehwan,Koh, Jin-Sin,Park, Jeong Rang,Jeong, Young-Hoon,Ahn, Jong Hwa,Jang, Jeong Yoon,Kwak, Choong Hwan,Park, Yongwhi,Jeong, Myung Ho,Kim, Young Jo,Cho, Myeong Cha The Korean Society of Cardiology 2018 Korean Circulation Journal Vol.48 No.2
<P><B>Background and Objectives</B></P><P>After the first acute myocardial infarction (AMI), a considerable proportion of patients are newly diagnosed with diabetes mellitus (DM). However, in AMI, controversy remains regarding the disparity in prognosis between previously diagnosed DM (known-DM) and newly diagnosed DM (new-DM).</P><P><B>Methods</B></P><P>The study included 10,455 patients with AMI (non-DM, 6,236; new-DM, 659; known-DM, 3,560) admitted to one of 15 participating centers in Korea between November 2011 and January 2016 (average follow-up, 523 days). We compared the characteristics and clinical course of patients with known-DM and those with new- or non-DM.</P><P><B>Results</B></P><P>Compared to patients with known-DM, those with new-DM or non-DM were younger, more likely to be male, and less likely to have hypertension, dyslipidemia, prior stroke, angina, or myocardial infarction. Compared to patients with new-DM or non-DM (reference), those with known-DM had higher risks of major adverse cardiac events (hazard ratio [HR], 1.20; 95% confidence interval [CI], 1.06–1.35; p=0.004), cardiac death (HR, 1.26; 95% CI, 1.01–1.57; p=0.042), and congestive heart failure (HR, 1.58; 95% CI, 1.20–2.08). Unlike known-DM, new-DM did not increase the risk of cardiac events (including death).</P><P><B>Conclusions</B></P><P>Known-DM was associated with a significantly higher risk of cardiovascular events after AMI, while new-DM had a similar risk of cardiac events as that noted for non-DM. There were different cardiovascular outcomes according to diabetes status in patients with AMI.</P>
Hua Hong,Jeong Rang Jo,Ji Hyeon Yeon,Jun Tack Hong,Kyung Hwan Jung,Sun Kyun Yoo,Byeong Churl Jang 한국미생물 · 생명공학회 2011 Journal of microbiology and biotechnology Vol.21 No.2
The study objective was to prepare biodegradable branched dextran microspheres encapsulated with His-tagged interferon-alpha (BDM-hIFN-α) and evaluate its activity in vitro and in vivo. The glycidyl methacrylate derivatized dextrans (Dex-GMA) as precursor was primarily synthesized by substituting hydroxyl groups of either the branched or linear type of dextran with GMA. Dex-GMA microspheres loaded with hIFN-α was then prepared by the water-in-water emulsion technique. In vitro release and Western blotting experiments demonstrated the retained activity of hIFN-α released from branched dextran microspheres at 24 h by inducing phosphorylation of signal transducer and activator transcription-1 (STAT-1), a down-stream effector of IFN-α, in HepG2 cells. Animal data further revealed a peak of plasma levels of IFN-α in rats injected intravenously with BDM-hIFN-α at 10 min post-injection, but a sharp decline at 2 h. High plasma levels of neopterin, a plasma protein induced by IFN-α, were also detected in rats injected with BDM-hIFN-α at 10 min post-injection. Notably, plasma levels of neopterin remained high at 4 h, but largely declined thereafter.
Human ERV3-1 env protein expression in various human tissues and tumours
Kang, Yun-Jeong,Jo, Jin-Ok,Ock, Mee Sun,Chang, Hee-Kyung,Baek, Kyung-Wan,Lee, Ja-Rang,Choi, Yung Hyun,Kim, Wun-Jae,Leem, Sun-Hee,Kim, Heui-Soo,Cha, Hee-Jae BMJ Publishing Group Ltd 2014 Journal of clinical pathology Vol.67 No.1