Evaluation of micro RNA146 a Mimic Therapy on

• Non-alcoholic fatty liver disease (NAFLD) is a common chronic liver disease with

3 https: //www. taconic. com/taconic-insights/metabolic-disease/what-is-NASH. html

Methionine Choline Deficient Diet in Rodents MCD diet VLDL Fatty acid NASH 4 https:

What is db/db mouse ？ • The db/db mouse is a model of obesity,

The process of micro. RNA formation and function? micro. RNA-146 a-5 p 3’-UGAGAACUGAAUUCCAUGGGUU-5’ 6

Methods 1. NASH is induced by feeding the db/db mice with MCD diet for

The mi. R-146 a-5 p mimic injection reduced mice body weight (A) and liver

The mi. R-146 a-5 p mimic injection reduced mice ALT (A) and (B) T-CHO

The mi. R-146 a-5 p mimic injection decreased CD 68 on kupffer cells of

The mi. R-146 a-5 p mimic injection decreased lipid distributions of liver tissues in

The mi. R-146 a-5 p mimic injection reduced MCD-induced inflammations. (A) NOX 4 (B)

The mi. R-146 a-5 p had identified to antisense with 3’ UTR of MALAT-1

Conclusion • These results suggested that mi. R-146 a-5 p maybe a novel target

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Evaluation of micro. RNA-146 a Mimic Therapy on Nonalcoholic Steatohepatitis (NASH) 報告者: 辛芊慧指導教授: 羅婉瑜

• Non-alcoholic fatty liver disease (NAFLD) is a common chronic liver disease with estimates of incidence around 25% worldwide. • NASH represents the more severe end of the NAFLD spectrum, with inflammation and fibrosis which can progress to cirrhosis and even liver cancer. 2 metabolismclinicalandexperimental 65 (2016)1038– 1048

3 https: //www. taconic. com/taconic-insights/metabolic-disease/what-is-NASH. html

Methionine Choline Deficient Diet in Rodents MCD diet VLDL Fatty acid NASH 4 https: //slideplayer. com/slide/8883456/

What is db/db mouse ？ • The db/db mouse is a model of obesity, type 2 DM and dyslipidemia. 1. Type 2 DM and obesity research 2. Wound healing research 3. Endocrine research 4. Metabolic research 5. Reproductive physiological research 5

The process of micro. RNA formation and function? micro. RNA-146 a-5 p 3’-UGAGAACUGAAUUCCAUGGGUU-5’ 6

Methods 1. NASH is induced by feeding the db/db mice with MCD diet for 4 weeks. 2. Mirco. RNA-146 a-5 p mimic injection for 3 weeks (10μg/mice/week). 3. Blood biochemical analysis of alanine transaminase (ALT) and total cholesterol (T-CHO) from serum. 4. Immunohistochemistry (IHC) staining of CD 68 on kupffer cells and oil red o staining of lipid from liver tissues. 5. Western blotting of NADPH oxidase 4 (NOX 4), interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF-α) from liver tissues. . 6. Real-time polymerase chain reaction (Q-PCR) of metastasis associated lung adenocarcinoma transcript 1 (MALAT 1) from liver tissues. 7

The mi. R-146 a-5 p mimic injection reduced mice body weight (A) and liver weight (B) in NASH animal models. (A ) (B) * 8

The mi. R-146 a-5 p mimic injection reduced mice ALT (A) and (B) T-CHO in NASH animal models. 9

The mi. R-146 a-5 p mimic injection decreased CD 68 on kupffer cells of liver tissues in NASH mice. 10

The mi. R-146 a-5 p mimic injection decreased lipid distributions of liver tissues in NASH mice. 11

The mi. R-146 a-5 p mimic injection reduced MCD-induced inflammations. (A) NOX 4 (B) IL-6 * (C) TNF-α 12

The mi. R-146 a-5 p had identified to antisense with 3’ UTR of MALAT-1 gene. Thus, the mi. R-146 a-5 p injection was demonstrated to downregulate the MALAT-1 gene expression level of liver in NASH mice. * 13

Conclusion • These results suggested that mi. R-146 a-5 p maybe a novel target for therapy of NASH via MALAT 1 gene. 14

Thank you for your attentions.