Aquaporin 5 maintains lens transparency by regulating the lysosomal pathway using circRNA.
Aquaporin 5 maintains lens transparency by regulating the lysosomal pathway using circRNA.
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DOI：
10.1111/jcmm.17679
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发表时间：
2023-03
影响因子：
5.3
通讯作者：
中科院分区：
文献类型：
--
作者：
透镜透明、无血管、有弹性，包裹在透明囊内。AQP 5 −/−小鼠的透镜混浊度比野生型（AQP 5 +/+）小鼠增加更多。在这项研究中，我们探讨了环状RNA（circRNA）和转录因子HSF 4在水通道蛋白5（AQP 5）敲除（AQP 5 −/−）小鼠透镜混浊中的潜在功能作用。自噬在AQP 5 −/−小鼠的透镜组织中受损。基于透射电子显微镜分析，与AQP 5 +/+小鼠相比，AQP 5 −/−小鼠透镜上皮细胞中的自噬溶酶体增加。通过高通量测序获得小鼠透镜的遗传信息，然后分析下游基因。通过对差异表达的circRNA进行生物信息学分析，构建与溶酶体途径相关的circRNA-miRNA-mRNA网络。基于TargetScan网站的预测，并通过双荧光素酶报告基因检测和RNA免疫沉淀-qPCR验证，我们发现circRNA（Chr 16：33421321 - 33468183+）通过海绵状microRNA（miR-149 - 5 p）抑制HSF 4的功能，下调溶酶体相关mRNA的正常表达。自噬溶酶体的积聚可能是AQP 5 −/−小鼠透镜发育异常的原因之一。
The lens is transparent, non‐vascular, elastic and wrapped in a transparent capsule. The lens oppacity of AQP5−/− mice was increased more than that of wild‐type (AQP5+/+) mice. In this study, we explored the potential functional role of circular RNAs (circRNAs) and transcription factor HSF4 in lens opacity in aquaporin 5 (AQP5) knockout (AQP5−/−) mice. Autophagy was impaired in the lens tissues of AQP5−/− mice. Autophagic lysosomes in lens epithelial cells of AQP5−/− mice were increased compared with AQP5+/+ mice, based on analysis by transmission electron microscopy. The genetic information of the mice lens was obtained by high‐throughput sequencing, and then the downstream genes were analysed. A circRNA‐miRNA‐mRNA network related to lysosomal pathway was constructed by the bioinformatics analysis of the differentially expressed circRNAs. Based on the prediction of the TargetScan website and the validation by dual luciferase reporter assay and RNA immunoprecipitation‐qPCR, we found that circRNA (Chr16: 33421321‐33468183+) inhibited the function of HSF4 by sponging microRNA (miR‐149‐5p), and it downregulated the normal expression of lysosome‐related mRNAs. The accumulation of autophagic lysosome may be one of the reasons for the abnormal development of the lens in AQP5−/− mice.
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影响因子：
5.5
作者：
Anand D;Al Saai S;Shrestha SK;Barnum CE;Chuma S;Lachke SA
通讯作者：
Lachke SA
影响因子：
3.7
作者：
Caceres A;Shang F;Wawrousek E;Liu Q;Avidan O;Cvekl A;Yang Y;Haririnia A;Storaska A;Fushman D;Kuszak J;Dudek E;Smith D;Taylor A
通讯作者：
Taylor A
DOI：
10.1016/0309-1651(86)90027-5
发表时间：
1986-07-01
期刊：
CELL BIOLOGY INTERNATIONAL REPORTS
影响因子：
--
作者：
DEWAAL, EJ;VREELINGSINDELAROVA, H;JAMES, J
通讯作者：
JAMES, J
影响因子：
4
作者：
Liu, Yaning;Di, Guohu;Chen, Peng
通讯作者：
Chen, Peng
影响因子：
1.7
作者：
Kechin, Andrey;Boyarskikh, Uljana;Filipenko, Maxim
通讯作者：
Filipenko, Maxim