Cerebral furin deficiency causes hydrocephalus in mice

作者全名："Xie, Shiqi; Xie, Xiaoyong; Tang, Jing; Luo, Biao; Chen, Jian; Wen, Qixin; Zhou, Jianrong; Chen, Guojun"

作者地址："[Xie, Shiqi; Zhou, Jianrong] Chongqing Med Univ, Nursing Coll, Chongqing 400016, Peoples R China; [Xie, Xiaoyong; Tang, Jing; Luo, Biao; Chen, Jian; Wen, Qixin; Chen, Guojun] Chongqing Med Univ, Affiliated Hosp 1, Dept Neurol,Chongqing Key Lab Major Neurol & Menta, Chongqing Key Lab Neurol, Chongqing 400016, Peoples R China"

通信作者："Zhou, JR (通讯作者)，Chongqing Med Univ, Nursing Coll, Chongqing 400016, Peoples R China.; Chen, GJ (通讯作者)，Chongqing Med Univ, Affiliated Hosp 1, Dept Neurol,Chongqing Key Lab Major Neurol & Menta, Chongqing Key Lab Neurol, Chongqing 400016, Peoples R China."

来源：GENES & DISEASES

ESI学科分类：MOLECULAR BIOLOGY & GENETICS

WOS号：WOS:001150335300001

JCR分区：Q1

影响因子：6.9

年份：2024

卷号：11

期号：3

开始页：　

结束页：　

文献类型：Article

关键词：Astrocyte; Ciliogenesis; Conditional knockout; Ependymal; Furin; Hydrocephalus; Proteomics

摘要："Furin is a pro-protein convertase that moves between the trans-Golgi network and cell surface in the secretory pathway. We have previously reported that cerebral overexpression of furin promotes cognitive functions in mice. Here, by generating the brain-specific furin conditional knockout (cKO) mice, we investigated the role of furin in brain development. We found that furin deficiency caused early death and growth retardation. Magnetic resonance imaging showed severe hydrocephalus. In the brain of furin cKO mice, impaired ciliogenesis and the derangement of microtubule structures appeared along with the down-regulated expression of RAB28, a ciliary vesicle protein. In line with the widespread neuronal loss, ependymal cell layers were damaged. Further proteomics analysis revealed that cell adhesion molecules including astrocyte-enriched ITGB8 and BCAR1 were altered in furin cKO mice; and astrocyte overgrowth was accompanied by the reduced expression of SOX9, indicating a disrupted differentiation into ependymal cells. Together, whereas alteration of RAB28 expression correlated with the role of vesicle trafficking in ciliogenesis, dysfunctional astrocytes might be involved in ependymal damage contributing to hydrocephalus in furin cKO mice. The structural and molecular alterations provided a clue for further studying the potential mechanisms of furin. (c) 2023 The Authors. Publishing services by Elsevier B.V. on behalf of KeAi Communications Co., Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons. org/licenses/by-nc-nd/4.0/)."

基金机构："National Nat- ural Science Foundation of China [81971030, 82271461]"

基金资助正文："<BOLD>Funding</BOLD> This work was supported by grants from the National Nat- ural Science Foundation of China (No. 81971030, 82271461 to GJ Chen) ."