公司新聞

吉瑪慢病毒再次助力我國優(yōu)秀科學(xué)家登頂國際頂級期刊《CELL》

2020年9月14日,中山大學(xué)孫逸仙紀念醫院 蘇士成博士、許小丁博士及中山大學(xué)附屬第三醫院 高志良教授作為共同通訊作者,在國際頂尖學(xué)術(shù)期刊? Cell 在線(xiàn)發(fā)表題為:Targeting Mitochondria-Located circRNA SCAR Alleviates NASH via Reducing mROS Output 的研究論文。該研究確定了一種 線(xiàn)粒體特異性circRNA——SCAR,在 非酒精性脂肪性肝炎(NASH)中表達下調,向線(xiàn)粒體特異性遞送SCAR,可降低線(xiàn)粒體活性氧 (mROS)輸出,減輕炎癥,可作為NASH的治療靶標。

非酒精性脂肪性肝炎(NASH)是 非酒精性脂肪性肝?。∟AFLD)的炎癥亞型,伴有肝脂肪變性以及肝細胞損傷和炎癥的證據,伴或不伴肝纖維化。隨著(zhù)時(shí)間的推移, NASH可能進(jìn)展為肝硬化、終末期肝病或需要肝移植。非酒精性脂肪性肝炎患者的肝病致殘率和病死率顯著(zhù)高于單純性脂肪肝。

線(xiàn)粒體(mitochondrion),是細胞的“ 能量工廠(chǎng)”,線(xiàn)粒體發(fā)揮重要的細胞功能,通過(guò)氧化磷酸化 (OXPHOS)調節能量供應,執行細胞死亡以及Ca離子和活性氧(ROS)的細胞內信號轉導,線(xiàn)粒體 在免疫代謝疾病中也起到了關(guān)鍵作用。

研究團隊通過(guò)對非酒精性脂肪性肝炎(NASH)患者肝成纖維細胞的circRNA表達譜分析,發(fā)現線(xiàn)粒體circRNA占NASH成纖維細胞下調circRNA的相當一部分。觀(guān)察到位于線(xiàn)粒體中的 circRNA——SCAR,抑制線(xiàn)粒體活性氧 (mROS)輸出和成纖維細胞活化。由PGC-1α介導的circRNA SCAR與ATP5B結合,并通過(guò)構建慢病毒shRNA干擾阻斷CypD-mPTP相互作用而關(guān)閉 線(xiàn)粒體通透轉運孔道(mPTP)。脂質(zhì)超載通過(guò)內質(zhì)網(wǎng)應激誘導的 C/EBP-同源蛋白(CHOP)抑制PGC-1α。動(dòng)物體內實(shí)驗也表明,靶向circRNA SCAR可減輕高脂飲食引起的肝硬化和胰島素抵抗。而在臨床上,circRNA SCAR與脂肪變性到NASH的進(jìn)展有關(guān)。

通過(guò)該研究,我國科學(xué)家又進(jìn)步確定了一種線(xiàn)粒體中的新型circRNA——SCAR,可作為非酒精性脂肪性肝炎(NASH)的治療靶標,為我們今后攻克該疾病提供了新的研究方向。

?
?


Figure 5. circRNA SCAR Shuts Down mPTP by Preventing CypD-mPTP Interaction

(A) Normal fibroblasts were treated with palmitate in the presence of mito-NP containing empty vectors (Vector), wild-type (SCAR), or mutated (SCAR-mut) circRNA SCAR overexpression vectors. Their mPTP opening was measured by calcein loading/CoCl2 quenching (n = 4 patients).

(B) In vitro RNA/protein interaction assay between recombinant ATP5B and indicated biotin-labeled circRNAs (n = 3).

(C) Normal fibroblasts were treated with palmitate in the presence of mito-NP containing wild-type or mutated circRNA SCAR overexpression vectors. Representative western blots of CypD and ATP5B (subunit of ATP synthase) in the ATP synthase-immunoprecipitated lysates are shown (n = 3 patients).

(D–G) Normal fibroblasts were treated with palmitate in the presence of mito-NP containing wild-type or mutated circRNA SCAR overexpression vectors. In some experiments, fibroblasts were pre-transduced with CypD-shRNAs.

(D) mPTP opening (upper) and ΔΨm (lower) were measured by calcein loading/CoCl2 quenching and JC-1 staining, respectively (n = 3 patients).

(E) Cytosolic ROS levels were detected by cytoORP via confocal microscopy. The 405/488 nm excitation ratio was quantitated (n = 5 patients).

(F) Fibroblast contractility in collagen matrices (n = 3 patients).

(G) Indicated cytokines were examined by ELISA (n = 4 patients).

注:材料方法中shRNA and siRNA Mediated Silencing

For shRNA transduction, a lentiviral vector plasmid pLKO.1-puro (GenePharma Inc, Shanghai, China) was used to construct the stable clones.?

吉瑪基因病毒產(chǎn)品近幾年已經(jīng)連續多次助力我國科學(xué)家在頂級期刊CNS上發(fā)表重要科學(xué)論文(參見(jiàn)相關(guān)鏈接https://mp.weixin.qq.com/s/PdkI8YelrpYLRupy-lFz9Q)。近期我們又推出了新的產(chǎn)品方案和促銷(xiāo)方案,歡迎大家積極關(guān)注索取相關(guān)產(chǎn)品和服務(wù)信息。吉瑪基因是您攀登科學(xué)高峰的永久忠實(shí)伙伴。




參考文獻

1. Zhao et al., Targeting Mitochondria-Located circRNA SCAR Alleviates NASH via Reducing mROS Output, Cell (2020), https://doi.org/10.1016/j.cell.2020.08.009
2. C.Y. Yu et al.,The circular RNA circBIRC6 participates in the molecular circuitry controlling human pluripotency. Nat. Commun., 8 (2017), p. 1149


?
人妻互换免费中文字幕,五月综合激情婷婷六月,和少妇高潮30p,男女啪啪120秒试看免费,公i公在厨房要了我在线观看 南靖县| 大余县| 大理市| 乌海市| 福安市| 汶上县| 抚松县| 青海省| 台北县| 富宁县| 龙泉市| 金秀| 英山县| 开鲁县| 屏南县| 阿合奇县| 郸城县| 麦盖提县| 化德县| 铁岭市| 临澧县| 曲水县| 历史| 额尔古纳市| 任丘市| 鄂托克前旗| 宁海县| 全椒县| 稷山县| 大安市| 泰和县| 晋州市| 怀来县| 黄陵县| 灌云县| 苏尼特右旗| 久治县| 武宁县| 工布江达县| 南昌市| 昭平县| http://444 http://444 http://444 http://444 http://444 http://444