Lysophosphatidic acid increases mesangial cell proliferation in models of diabetic nephropathy via Rac1/MAPK/KLF5 signaling

Kim, Donghee,Li, Hui Ying,Lee, Jong Han,Oh, Yoon Sin,Jun, Hee-Sook Nature Publishing Group UK 2019 Experimental and molecular medicine Vol.51 No.2

<▼1><P>Mesangial cell proliferation has been identified as a major factor contributing to glomerulosclerosis, which is a typical symptom of diabetic nephropathy (DN). Lysophosphatidic acid (LPA) levels are increased in the glomerulus of the kidney in diabetic mice. LPA is a critical regulator that induces mesangial cell proliferation; however, its effect and molecular mechanisms remain unknown. The proportion of α-SMA<SUP>+</SUP>/PCNA<SUP>+</SUP> cells was increased in the kidney cortex of <I>db/db</I> mice compared with control mice. Treatment with LPA concomitantly increased the proliferation of mouse mesangial cells (SV40 MES13) and the expression of cyclin D1 and CDK4. On the other hand, the expression of p27<SUP>Kip1</SUP> was decreased. The expression of Krüppel-like factor 5 (KLF5) was upregulated in the kidney cortex of <I>db/db</I> mice and LPA-treated SV40 MES13 cells. RNAi-mediated silencing of KLF5 reversed these effects and inhibited the proliferation of LPA-treated cells. Mitogen-activated protein kinases (MAPKs) were activated, and the expression of early growth response 1 (Egr1) was subsequently increased in LPA-treated SV40 MES13 cells and the kidney cortex of <I>db/db</I> mice. Moreover, LPA significantly increased the activity of the Ras-related C3 botulinum toxin substrate (Rac1) GTPase in SV40 MES13 cells, and the dominant-negative form of Rac1 partially inhibited the phosphorylation of p38 and upregulation of Egr1 and KLF5 induced by LPA. LPA-induced hyperproliferation was attenuated by the inhibition of Rac1 activity. Based on these results, the Rac1/MAPK/KLF5 signaling pathway was one of the mechanisms by which LPA induced mesangial cell proliferation in DN models.</P></▼1><▼2><P><B>Kidney disease: Mechanisms of diabetes-related damage</B></P><P>A potent molecular mediator of diabetic kidney disease induces its pathogenic effects via proteins that could be targeted with future drug therapies. Yoon Sin Oh
from Eulji University in Seongnam-si and Hee-Sook Jun from Gachon University in Incheon, both in South Korea, and colleagues treated certain cells found in the kidney’s glomerulus, the organ’s filtering unit, with a signaling molecule called lysophosphatidic acid (LPA) that is elevated in the blood of diabetic mice. They showed that LPA stimulated cellular proliferation and boosted the expression of proteins involved in regulating the cell cycle and a multipurpose signaling pathway. They then inhibited the activity of these proteins to prevent the kidney cells’ hyperproliferation, both in cell culture and in diabetic mice. The results highlight the potential of blocking mediators of LPA signaling to treat kidney-related complications of diabetes.</P></▼2>

MMSE를 이용한 도시지역 노인들의 인지기능검사 성적

오민아,신윤오,이태용,김정선 충남대학교 의학연구소 2003 충남의대잡지 Vol.30 No.2

This study was performed to assess the degree of cognitive function impairment by MMSE performances and the effects. Data was collected by interviewers from 1,325 elderly people in Seogu, Daejeon city from June to July, 2002 and the collected data were analysed by SPSSWIN(ver 10.0). The results of analysis were as follows. The mean score of MMSE was 24.16±4.36 and significantly lower in female, in the older group and in the non-educated group. The subset score of MMSE were significantly lower in female group about each items: orientation in time and place, registration, attention/calculation, language except recall. And the scores were significantly lower in the older group and non-educated group about the all items of MMSE. In conclusion, sex, age and education showed significant effects on total and subset MMSE score. Cognitive function decline were higher in female sex, older age group and non-educated group. Therefore, those three factor are thought to be one of important risk factors for development of dementia because MMSE examination is useful instrument for evaluation of elderly dementia.

노인의 영적 간호요구

최미혜,김경희,김귀옥,김기숙,김수강,김정신,김춘숙,노흥진,박지연,성혜연,오명선,이선희,이원옥,이윤영,이현수,장명재,차혜경,채정선,홍상희 중앙대학교 의과대학 간호학과 간호과학연구소 2001 중앙간호논문집 Vol.5 No.1

This study was designed to exam the aged's needs for spiritual nursing care. The purpose was to serve as a basis for the development of spiritual nursing practice. The major findings are as follows : 1. The degree of needs for spiritual nursing care as area was that needs of love and relationship mean 22.0, needs of meaning and object mean 28.2, needs of forgiving mean 13.5. Total needs for spiritual nursing care mean 63.7, which was on the upper middle level. The needs of meaning and object was rated highest. 2. Among the general characteristics of the subjects, needs of love and relatiohship wasn't significanlty different. 3. Among the general characteristics of the subjects, needs of meaning and object was significantly different according to two factors : age(F=7.260, p=0.001), religion(F=5.275, p=0.001). Higher needs of meaning and object was possessed by the older than the younger, by the one who have religion than the other. 4. Among the general characteristics of the subjects, four factors made a significantly difference to needs of forgiving : sex(t=-2.851, p=0.006), age(F=8.201, p=0.001), religion(F=6.928, p=0.000), disease(t=2.327, p=0.024). Higher needs of forgiving was possessed by man than woman, by the older than the younger, by the one who have religion than the other, by the one who have disease than the other.

Effects of Glucagon-Like Peptide-1 on Oxidative Stress and Nrf2 Signaling

Oh, Yoon Sin,Jun, Hee-Sook MDPI 2018 INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES Vol.19 No.1

<P>Oxidative cellular damage caused by free radicals is known to contribute to the pathogenesis of various diseases such as cancer, diabetes, and neurodegenerative diseases, as well as to aging. The transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2) and Kelch-like ECH-associated protein1 (Keap1) signaling pathways play an important role in preventing stresses including oxidative and inflammatory stresses. Nrf2 is a master regulator of cellular stress responses, induces the expression of antioxidant and detoxification enzymes, and protects against oxidative stress-induced cell damage. Glucagon-like peptide-1 (GLP-1) is an incretin hormone, which was originally found to increase insulin synthesis and secretion. It is now widely accepted that GLP-1 has multiple functions beyond glucose control in various tissues and organs including brain, kidney, and heart. GLP-1 and GLP-1 receptor agonists are known to be effective in many chronic diseases, including diabetes, via antioxidative mechanisms. In this review, we summarize the current knowledge regarding the role of GLP-1 in the protection against oxidative damage and the activation of the Nrf2 signaling pathway.</P>

Exendin-4 inhibits glucolipotoxic ER stress in pancreatic β cells via regulation of SREBP1c and C/EBPβ transcription factors

Oh, Yoon Sin,Lee, Youn-Jung,Kang, Yup,Han, Jaeseok,Lim, Oh-Kyung,Jun, Hee-Sook Journal of Endocrinology, Ltd. [etc.] 2013 The Journal of endocrinology Vol.216 No.3

<P>Prolonged exposure to high glucose (HG) and palmitate (PA) results in increased ER stress and subsequently induces β-cell apoptosis. Exendin-4, a glucagon-like peptide-1 agonist, is known to protect β cells from toxicity induced by cytokines, HG, or fatty acids by reducing ER stress. However, the detailed molecular mechanisms for this protective effect are still not known. In this study, we investigated the role of exendin-4 in the inhibition of glucolipotoxicity-induced ER stress and β-cell apoptosis. Exendin-4 treatment protected INS-1 β cells from apoptosis in response to HG/PA (25 mM glucose+400 μM PA). HG/PA treatment increased cleaved caspase-3 and induced ER stress maker proteins such as PERK (EIF2AK3), ATF6, and phosphorylated forms of PERK, eIF2α, IRE1α (ERN1), and JNK (MAPK8), and these increases were significantly inhibited by exendin-4 treatment. HG/PA treatment of INS-1 cells increased SREBP1 (SREBF1) protein and induced its nuclear translocation and subsequently increased C/EBPβ (CEBPB) protein and its nuclear translocation. Exendin-4 treatment attenuated this increase. Knockdown of <I>SREBP1c</I> reduced the activation of <I>C/EBP</I><I>β</I> and also blocked the expression of ER stress markers induced by HG/PA treatment. Our results indicate that exendin-4 inhibits the activation of SREBP1c and C/EBPβ, which, in turn, may reduce glucolipotoxicity-induced ER stress and β-cell apoptosis.</P>

Modulation of Insulin Sensitivity and Caveolin-1 Expression by Orchidectomy in a Nonobese Type 2 Diabetes Animal Model

Oh, Yoon Sin,Lee, Tae Sup,Cheon, Gi Jeong,Jang, Ik-Soon,Jun, Hee-Sook,Park, Sang Chul Springer (Biomed Central Ltd.) 2011 Molecular Medicine Vol. No.

Regulation of insulin response in skeletal muscle cell by caveolin status

Oh, Yoon Sin,Cho, Kyung A.,Ryu, Sung Jin,Khil, Lee-Yong,Jun, Hee-Sook,Yoon, Ji-Won,Park, Sang Chul Wiley Subscription Services, Inc., A Wiley Company 2006 Journal of cellular biochemistry Vol.99 No.3

<P>Recent studies on the role of caveolin-1 in adipocytes showed that caveolin has emerged as an important regulatory element in insulin signaling but little is known on its role in skeletal muscle cells. In this study, we demonstrate for the first time that caveolin-1 plays a crucial role in insulin dependent glucose uptake in skeletal muscle cells. Differentiation of L6 skeletal muscle cells induce the expression of caveolin-1 and caveolin-3 with partial colocalization. However in contrast to adipocytes, phosphorylation of insulin receptor β (IRβ) and Akt/Erk was not affected by the respective downregulation of caveolin-1 or caveolin-3 in the muscle cells. Moreover, the phosphorylation of IRβ was detected not only in the caveolae but also in the non-caveolae fractions of the muscle cells despite the interaction of IRβ with caveolin-1 and caveolin-3. These data implicate the lack of relationship between caveolins and IRβ pathway in the muscle cells, different from the adipocytes. However, glucose uptake was reduced specifically by downregulation of caveolin-1, but not that of caveolin-3. Taken together, these observations suggest that caveolin-1 plays a crucial role in glucose uptake in differentiated muscle cells and that the regulation of caveolin-1 expression may be an important mechanism for insulin sensitivity, implying the role of muscle cells for type 2 diabetes. J. Cell. Biochem. 99: 747–758, 2006. © 2006 Wiley-Liss, Inc.</P>

인간 전립선 암세포인 TSU - Pr1에서 trans - 10, cis - 12 Conjugated Linoleic Acid에 의한 Apoptosis 유발과 Bcl - 2 단백질의 발현억제

오윤신(Yoon Sin Oh),김은지(Eun Ji Kim),이상곤(Sang Gon Lee),정차권(Cha-Kwon Chung),강일준(Il-Jun Kang),신현경(Hyun Kyung Shin),윤정한(Jung H. Y. Park) 한국식품영양과학회 2002 한국식품영양과학회지 Vol.31 No.6

CLA 이성체 mixture와 trans-10,cis-12 CLA는 살아있는 TSU-Pr1 세포 수를 감소시키는 반면 LA와 cis-9,trans-11 CLA는 세포 수에 아무런 효과가 없었다. 세포 수를 감소시키는 CLA 이성체 mixture와 trans-10,cis-12 CLA는 apoptotic cell death를 유도하는 것을 관찰하였고, 특히 trans-10,cis-12CLA는 Bcl-2/Bax 비율을 감소시켰다. Trans-10,cis-12 CLA에 의해 Bax와 Bcl-2 mRNA의 수준이 변하지 않았으므로 이 지방산에 의한 Bcl-2의 변화는 mRNA 전사 후에 일어나는 단계에서 일어난다고 결론지을 수 있다. 이로써 CLA에 의한 세포증식 억제는 부분적으로 TSU-Pr1 세포의 apoptosis를 유도함으로서 이루어지는 것이라 할 수 있다. Conjugated linoleic acid (CLA) is a collective term for a class of positional and geometric conjugated dienoic isomers of linoleic acid (LA) and has anti-cancer activity in experimental animals. We have previously observed that an isomeric mixture of CLA and trans-10,cis-12 (t10c12) inhibited cell growth in a dose-dependent manner, whereas LA and cis-9,trans-11 (c9t11) had no effect. The present study examined whether the CLA mixture and t10c12 induce apoptotic cell death. TSU-Pr1 cells were incubated for three days in serum-free medium in the absence or presence of individual fatty acids, and the DNA fragmentation assay was performed. Cells treated with the CLA mixture or t10c12 produced a distinct oligonucleosomal ladder with different sizes of DNA fragments, a typical characteristic of cells undergoing apoptosis. By contrast, LA and c9t11 had no effect. Western immunoblot analysis of total lysates revealed that t10c12 reduced anti-apoptotic, 26 kDa, Bcl-2 protein levels by 49±8% compared with controls, whereas this CLA isomer did not alter pro-apoptotic, 21 kDa, Bax protein levels. These results suggest that growth inhibitory effect of the t10c12 CLA isomer may, at least in part, be attributed to increased apoptotic death in TSU-Pr1 cells.

Conjugated Linoleic Acid (CLA) 와 그 이성체가 전립선 암세포의 증식에 미치는 영향

오윤신(Oh Yoon Sin),김은지(Kim Eun Ji),김종우(Kim Jong Woo),김우경(Kim Woo Kyung),이현숙(Lee Hyun Sook),윤정한 (Yoon Jung Han) 韓國營養學會 2002 Journal of Nutrition and Health Vol.35 No.2

성장인자를 이용한 췌장 베타세포 재생연구의 최근 동향

오윤신 ( Yoon Sin Oh ),전희숙 ( Hee Sook Jun ) 한국조직공학과 재생의학회 2010 조직공학과 재생의학 Vol.7 No.2

Both type 1 and type 2 diabetes are characterized by β cell loss and dysfunction. Therefore, replenishment of functional beta cells by either transplantation, or in vivo β cell regeneration is a therapeutic option. β cell mass can be increased by promoting replication of existing cells, differentiation from stem/progenitor cells and inhibiting beta cell apoptosis. In this review, we will summarize the recent advances in in vivo regeneration of insulin- producing β cells with various growth factors such as betacellulin, glucagon-like peptide-1, gastrin, hepatocyte growth factor and prolactin.