Circular RNA circPSD3 alleviates hepatic fibrogenesis by regulating the miR-92b-3p/Smad7 axis.
Circular RNA circPSD3 alleviates hepatic fibrogenesis by regulating the miR-92b-3p/Smad7 axis.
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DOI：
10.1016/j.omtn.2021.01.007
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发表时间：
2021-03-05
期刊：
影响因子：
--
通讯作者：
Li J
中科院分区：
文献类型：
--
作者：
Bu FT;Zhu Y;Chen X;Wang A;Zhang YF;You HM;Yang Y;Yang YR;Huang C;Li J
最近，环状RNA（circRNA）经常被报道参与肝细胞癌（HCC）的发生和进展。然而，circRNA在肝纤维化（HF）中的作用仍不清楚。我们之前的高通量筛选揭示了四氯化碳 (CCl4) 诱导的 HF 小鼠中许多 circRNA 的变化。例如，与媒介物组相比，circPSD3（一种源自 Pleckstrin 和 Sec7 结构域 3 (PSD3) 基因的 circRNA）在 CCl4 诱导的 HF 小鼠的原代肝星状细胞 (HSC) 和肝组织中的表达显着下调。使用 AAV8-circPSD3 体内过表达 circPSD3 可阻止 CCl4 诱导的心力衰竭恶化，血清丙氨酸转氨酶 (ALT) 和天冬氨酸转氨酶 (AST) 含量、肝脏羟脯氨酸水平、胶原蛋白沉积以及促纤维化基因和促炎细胞因子水平降低表明。此外，体外功能丧失和功能获得分析表明，circPSD3 抑制 HSC 的激活和增殖。从机制上讲，circPSD3充当miR-92b-3p的海绵，随后促进Smad7的表达。总之，我们目前的研究结果揭示了 circPSD3 通过靶向 miR-92b-3p/Smad7 轴减轻肝纤维化的新机制，并且还表明 circPSD3 可能作为心力衰竭的潜在生物标志物。 Jun Li及其同事发现，circPSD3通过调节miR-92b-3p/Smad7轴来调节肝纤维化中HSC的活化和增殖。该研究提示了circPSD3在肝纤维化中的治疗潜力，为治疗肝纤维化提供了新思路。
Recently, circular RNAs (circRNAs) have been frequently reported to be involved in hepatocellular carcinoma (HCC) development and progression. However, the role of circRNAs in hepatic fibrosis (HF) is still unclear. Our previous high-throughput screen revealed changes in many circRNAs in mice with carbon tetrachloride (CCl4)-induced HF. For instance, the expression of circPSD3, a circRNA derived from the Pleckstrin and Sec7 domain-containing 3 (PSD3) gene, was considerably downregulated in primary hepatic stellate cells (HSCs) and liver tissues of mice with CCl4-induced HF compared to those in the vehicle group. In vivo overexpression of circPSD3 using AAV8-circPSD3 arrested the deterioration of CCl4-induced HF as indicated by reduced serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) content, liver hydroxyproline level, collagen deposition, and pro-fibrogenic gene and pro-inflammatory cytokine levels. Moreover, in vitro loss-of-function and gain-of-function analyses suggested that circPSD3 inhibited the activation and proliferation of HSCs. Mechanistically, circPSD3 served as a sponge for miR-92b-3p, subsequently promoting the expression of Smad7. In conclusion, our present findings reveal a novel mechanism by which circPSD3 alleviates hepatic fibrogenesis by targeting the miR-92b-3p/Smad7 axis, and they also indicate that circPSD3 may serve as a potential biomarker for HF. Jun Li and colleagues found that circPSD3 regulates the activation and proliferation of HSCs in hepatic fibrosis through modulating the miR-92b-3p/Smad7 axis. This study suggests the therapeutic potential of circPSD3 in hepatic fibrosis and provides a novel idea for treating hepatic fibrosis.
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DOI：
10.1007/s00018-017-2688-5
发表时间：
2018-03
期刊：
Cellular and molecular life sciences : CMLS
影响因子：
--
作者：
Holdt LM;Kohlmaier A;Teupser D
通讯作者：
Teupser D
影响因子：
5
作者：
Greene J;Baird AM;Brady L;Lim M;Gray SG;McDermott R;Finn SP
通讯作者：
Finn SP
DOI：
10.1073/pnas.1201840109
发表时间：
2012-06-12
影响因子：
11.1
作者：
Kisseleva, Tatiana;Cong, Min;Brenner, David A.
通讯作者：
Brenner, David A.
影响因子：
3.5
作者：
Martin, Jose-Ezequiel;Broen, Jasper C.;Martin, Javier
通讯作者：
Martin, Javier
影响因子：
16.6
作者：
Hyun J;Wang S;Kim J;Rao KM;Park SY;Chung I;Ha CS;Kim SW;Yun YH;Jung Y
通讯作者：
Jung Y