Inhibition of miR-34a-5p alleviates hypoxia-reoxygenation injury by enhancing autophagy in steatotic hepatocytes.
Inhibition of miR-34a-5p alleviates hypoxia-reoxygenation injury by enhancing autophagy in steatotic hepatocytes.
复制标题
抑制 miR-34a-5p 通过增强脂肪肝细胞的自噬来减轻缺氧-复氧损伤。
DOI：
10.1242/bio.033290
复制
发表时间：
2018-03-26
期刊：
影响因子：
2.4
通讯作者：
Li Q
中科院分区：
文献类型：
--
作者：
Li C;Wang K;Guo L;Sun H;Huang H;Lin X;Li Q
脂肪变性肝细胞缺氧-复氧（H/R）损伤与肝移植后肝功能障碍有关。microRNAs（miRs）在调节与H/R损伤相关的多种细胞生物学机制中发挥重要作用。然而，miR在脂肪变性肝细胞中调节H/R损伤的作用仍不清楚。我们建立了一个研究脂肪肝细胞H/R损伤的体外模型，并将miR-34 a-5 p鉴定为在H/R攻击下脂肪肝细胞中显著上调的miR。通过将miR-34 a-5 p模拟物和抑制剂转染到H/R攻击的脂肪变性肝细胞中来修饰miR-34 a-5 p表达。我们发现抑制miR-34 a-5 p可以减轻H/R诱导的细胞凋亡并促进脂肪变性肝细胞H/R后的增殖。而过表达miR-34 a-5 p则增强H/R诱导的细胞凋亡，抑制H/R后细胞增殖。通过检查自噬，我们的数据表明，miR-34 a-5 p抑制H/R-攻击的脂肪变性肝细胞中的自噬，诱导自噬部分地挽救了由miR-34 a-5 p模拟物诱导的H/R损伤的加重，而自噬的抑制削弱了miR-34 a-5 p抑制剂对H/R损伤的保护。总之，miR-34 a-5 p在夸大H/R损伤中至关重要，可能通过抑制脂肪变性肝细胞中的自噬。抑制miR-34 a可能是保护脂肪变性肝细胞免受H/R损伤的有希望的策略。总结：我们的研究建立了一个研究脂肪肝H/R损伤的体外模型，并表明MiR-34 a在加重H/R损伤中起重要作用，可能通过抑制脂肪变性肝细胞中的自噬。
Hypoxia-reoxygenation (H/R) injury in steatotic hepatocytes has been implicated in liver dysfunction after liver transplantation. MicroRNAs (miRs) play important roles in regulating several cell biology mechanisms related to H/R injury. However, the role of miRs in regulating H/R injury in steatotic hepatocytes is still unclear. We established an in vitro model for studying H/R injury in steatotic hepatocytes and identified miR-34a-5p as a miR that was substantially upregulated in steatotic hepatocytes under H/R challenge. MiR-34a-5p expression was modified by transfecting miR-34a-5p mimic and inhibitor into H/R-challenged steatotic hepatocytes. We found that inhibition of miR-34a-5p alleviated H/R-induced apoptosis and promoted post-H/R proliferation in steatotic hepatocytes. Whereas, overexpression of miR-34a-5p augmented H/R-induced apoptosis and prohibited post-H/R proliferation. By examining autophagy, our data demonstrated that miR-34a-5p suppressed autophagy in H/R-challenged steatotic hepatocytes, induction of autophagy partially rescued the exaggeration of H/R injury induced by miR-34a-5p mimic, while inhibition of autophagy impaired the protection of the miR-34a-5p inhibitor against H/R injury. In conclusion, miR-34a-5p is crucial in exaggerating H/R injury, likely by suppressing autophagy in steatotic hepatocytes. Inhibition of miR-34a may be a promising strategy to protect steatotic hepatocytes against H/R-injury. Summary: Our study establishes an in vitro model for studying H/R injury in fatty liver, and shows that MiR-34a plays an important role in worsening H/R injury, likely by suppressing autophagy in steatotic hepatocytes.
登录
查看更多内容
影响因子：
25.7
作者：
Pais R;Barritt AS 4th;Calmus Y;Scatton O;Runge T;Lebray P;Poynard T;Ratziu V;Conti F
通讯作者：
Conti F
MicroRNA-21 通过 Akt/mTOR 通路抑制 H9c2 细胞中的过度自噬，从而防止心脏缺氧/复氧损伤
影响因子：
5.3
作者：
Huang Z;Wu S;Kong F;Cai X;Ye B;Shan P;Huang W
通讯作者：
Huang W
miR-34a 下调 Bcl-2 表达介导棕榈酸酯诱导的 Min6 细胞凋亡
影响因子：
4.3
作者：
Lin X;Guan H;Huang Z;Liu J;Li H;Wei G;Cao X;Li Y
通讯作者：
Li Y
影响因子：
8
作者：
Leung, W. K. C.;Ching, A. K. K.;Wong, N.
通讯作者：
Wong, N.
DOI：
10.1111/j.1440-1746.2008.05733.x
发表时间：
2009-05-01
影响因子：
4.1
作者：
Ricchi, Matteo;Odoardi, Maria Rosaria;Loria, Paola
通讯作者：
Loria, Paola