<i>mTOR</i> mutation disrupts larval zebrafish tail fin regeneration via regulating proliferation of blastema cells and mitochondrial functions

作者全名：Xiao, Gongyi; Li, Xiangwei; Yang, Huiping; Zhang, Ruobin; Huang, Junlan; Tian, Yu; Nie, Mao; Sun, Xianding

作者地址：[Xiao, Gongyi; Li, Xiangwei; Nie, Mao; Sun, Xianding] Chongqing Med Univ, Affiliated Hosp 2, Ctr Joint Surg, Dept Orthoped Surg, 74 Linjiang Rd, Chongqing 400010, Peoples R China; [Yang, Huiping] Chongqing Med Univ, Affiliated Hosp 2, Dept Cardiol, 74 Linjiang Rd, Chongqing 400010, Peoples R China; [Zhang, Ruobin; Huang, Junlan; Tian, Yu] Army Med Univ, Daping Hosp, Res Inst Surg, Trauma Ctr,Combined Injury, Chongqing 400042, Peoples R China; [Tian, Yu] Chongqing Univ, Minist Educ, Coll Bioengn, Chongqing 400044, Peoples R China

通信作者：Nie, M; Sun, XD (通讯作者)，Chongqing Med Univ, Affiliated Hosp 2, Ctr Joint Surg, Dept Orthoped Surg, 74 Linjiang Rd, Chongqing 400010, Peoples R China.

来源：JOURNAL OF ORTHOPAEDIC SURGERY AND RESEARCH

ESI学科分类：CLINICAL MEDICINE

WOS号：WOS:001235336700003

JCR分区：Q1

影响因子：2.8

年份：2024

卷号：19

期号：1

开始页：　

结束页：　

文献类型：Article

关键词：mTOR; Zebrafish; Larvae fin; Regeneration; Mitochondrial fission; Ca2+

摘要：Background The larval zebrafish tail fin can completely regenerate in 3 days post amputation. mTOR, the main regulator of cell growth and metabolism, plays an essential role in regeneration. Lots of studies have documented the role of mTOR in regeneration. However, the mechanisms involved are still not fully elucidated. Materials and results This study aimed to explore the role and mechanism of mTOR in the regeneration of larval zebrafish tail fins. Initially, the spatial and temporal expression of mTOR signaling in the larval fin was examined, revealing its activation following tail fin amputation. Subsequently, a mTOR knockout (mTOR-KO) zebrafish line was created using CRISPR/Cas9 gene editing technology. The investigation demonstrated that mTOR depletion diminished the proliferative capacity of epithelial and mesenchymal cells during fin regeneration, with no discernible impact on cell apoptosis. Insight from SMART-seq analysis uncovered alterations in the cell cycle, mitochondrial functions and metabolic pathways when mTOR signaling was suppressed during fin regeneration. Furthermore, mTOR was confirmed to enhance mitochondrial functions and Ca2 + activation following fin amputation. These findings suggest a potential role for mTOR in promoting mitochondrial fission to facilitate tail fin regeneration. Conclusion In summary, our results demonstrated that mTOR played a key role in larval zebrafish tail fin regeneration, via promoting mitochondrial fission and proliferation of blastema cells.

基金机构：National Natural Science Foundation of China

基金资助正文：Not applicable.