Anp32b-deficiency suppresses ocular development by repression of Pax6.

IF 2 4区 医学 Q2 OPHTHALMOLOGY Ophthalmic Research Pub Date : 2024-11-06 DOI:10.1159/000542447
Yu-Sheng Wei, Hao-Ran Liu, Qian Yang, Zhe Zhi, Yun Yu
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Abstract

Introduction This study aims to elucidate the role and molecular mechanisms of acidic leucine-rich nuclear phosphoprotein 32kDa B (Anp32b)-deficiency in ocular development. Methods We used constitutive C57BL/6-derived Anp32b-/- mice to elucidate the role of Anp32b in ocular development, including the phenotype and proportion of eye malformation in different genotypes. RNA-Seq analysis and rescue experiments were performed to investigate the underlying mechanisms of Anp32b. Results Deletion of Anp32b contributes to severe defects in ocular development, including anophthalmia and microphthalmia. Moreover, Anp32b is highly expressed in the lens, and Anp32b-/- embryos with microphthalmia often exhibit severely impaired lens development. Mechanistically, ANP32B directly interacts with paired box protein 6 (PAX6), a master transcriptional regulator, and enhances its transcriptional activity. Overexpression of PAX6 partially but significantly reverses the inhibition of proliferation observed in ANP32B knockdown lens epithelial cells. Conclusions Our findings indicate that Anp32b-deficiency suppresses ocular development by repressing Pax6 and identify that Anp32b is a viable therapeutic target for ocular developmental defects.

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Anp32b缺陷通过抑制Pax6抑制眼球发育。
引言 本研究旨在阐明酸性富亮氨酸核磷蛋白32kDa B(Anp32b)缺陷在眼部发育中的作用和分子机制。方法 我们利用组成型C57BL/6衍生的Anp32b-/-小鼠来阐明Anp32b在眼部发育中的作用,包括不同基因型的表型和眼部畸形比例。通过RNA-Seq分析和拯救实验研究Anp32b的内在机制。结果 Anp32b缺失会导致严重的眼部发育缺陷,包括无眼症和小眼球症。此外,Anp32b在晶状体中高度表达,患有小眼症的Anp32b-/-胚胎往往表现出严重的晶状体发育障碍。从机制上讲,ANP32B 直接与成对盒蛋白 6(PAX6)(一种主转录调控因子)相互作用,并增强其转录活性。过表达 PAX6 可部分但显著地逆转 ANP32B 敲除后观察到的晶状体上皮细胞增殖抑制。结论 我们的研究结果表明,Anp32b缺陷通过抑制Pax6抑制眼球发育,并确定Anp32b是眼球发育缺陷的可行治疗靶点。
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来源期刊
Ophthalmic Research
Ophthalmic Research 医学-眼科学
CiteScore
3.80
自引率
4.80%
发文量
75
审稿时长
6-12 weeks
期刊介绍: ''Ophthalmic Research'' features original papers and reviews reporting on translational and clinical studies. Authors from throughout the world cover research topics on every field in connection with physical, physiologic, pharmacological, biochemical and molecular biological aspects of ophthalmology. This journal also aims to provide a record of international clinical research for both researchers and clinicians in ophthalmology. Finally, the transfer of information from fundamental research to clinical research and clinical practice is particularly welcome.
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