{"title":"tsRNA-3043a 通过靶向 FLT1 加速卵巢颗粒细胞的凋亡和衰老，从而导致卵巢早衰。","authors":"Jianzhen Huang, Fang Zeng, Hongxia Yi, Lixia Wan, Qinggang Xu","doi":"10.1007/s10735-024-10256-8","DOIUrl":null,"url":null,"abstract":"<div><p>Premature ovarian failure (POF) represents the pathological aging of the ovary. The tRNA-derived small fragments (tsRNAs) play significant roles in diseases; however, whether tsRNAs are involved in POF remains unknown. The cell and mice models of POF were established, and the tsRNAs profile in the ovarian tissues of POF mice was revealed through sequencing. The functions of tsRNA-3043a and its target gene <i>FLT1</i> in POF cells and mice were detected. POF mice were characterized by a decreased number of normal follicles, ovarian weight, SOD level, and serum contents of E2, LH, and FSH. A total of 81 tsRNAs were aberrantly expressed in the ovarian tissue of POF mice. The expression of tsRNA-3043a was up-regulated in POF mice. tsRNA-3043a mimics inhibited the proliferation and promoted apoptosis, lipid accumulation, and cellular senescence of ovarian granulosa KGN cells, as well as altered the transcriptome. tsRNA-3043a inhibitor had the opposite effect. tsRNA-3043a targets and binds to <i>FLT1.</i> Overexpression of <i>FLT1</i> protected KGN cells from pathological aging. tsRNA-3043a promotes the progression of POF by inhibiting <i>FLT1 in vitro</i> and <i>in vivo.</i> tsRNA-3043a targets FLT1 and promotes apoptosis and senescence of ovarian granulosa cells, leading to the progression of POF. This study provides a new target for pharmacological intervention in POF.</p></div>","PeriodicalId":650,"journal":{"name":"Journal of Molecular Histology","volume":"55 6","pages":"1147 - 1162"},"PeriodicalIF":2.9000,"publicationDate":"2024-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s10735-024-10256-8.pdf","citationCount":"0","resultStr":"{\"title\":\"tsRNA-3043a intensifies apoptosis and senescence of ovarian granulosa cells to drive premature ovarian failure by targeting FLT1\",\"authors\":\"Jianzhen Huang, Fang Zeng, Hongxia Yi, Lixia Wan, Qinggang Xu\",\"doi\":\"10.1007/s10735-024-10256-8\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><p>Premature ovarian failure (POF) represents the pathological aging of the ovary. The tRNA-derived small fragments (tsRNAs) play significant roles in diseases; however, whether tsRNAs are involved in POF remains unknown. The cell and mice models of POF were established, and the tsRNAs profile in the ovarian tissues of POF mice was revealed through sequencing. The functions of tsRNA-3043a and its target gene <i>FLT1</i> in POF cells and mice were detected. POF mice were characterized by a decreased number of normal follicles, ovarian weight, SOD level, and serum contents of E2, LH, and FSH. A total of 81 tsRNAs were aberrantly expressed in the ovarian tissue of POF mice. The expression of tsRNA-3043a was up-regulated in POF mice. tsRNA-3043a mimics inhibited the proliferation and promoted apoptosis, lipid accumulation, and cellular senescence of ovarian granulosa KGN cells, as well as altered the transcriptome. tsRNA-3043a inhibitor had the opposite effect. tsRNA-3043a targets and binds to <i>FLT1.</i> Overexpression of <i>FLT1</i> protected KGN cells from pathological aging. tsRNA-3043a promotes the progression of POF by inhibiting <i>FLT1 in vitro</i> and <i>in vivo.</i> tsRNA-3043a targets FLT1 and promotes apoptosis and senescence of ovarian granulosa cells, leading to the progression of POF. This study provides a new target for pharmacological intervention in POF.</p></div>\",\"PeriodicalId\":650,\"journal\":{\"name\":\"Journal of Molecular Histology\",\"volume\":\"55 6\",\"pages\":\"1147 - 1162\"},\"PeriodicalIF\":2.9000,\"publicationDate\":\"2024-09-30\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://link.springer.com/content/pdf/10.1007/s10735-024-10256-8.pdf\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Molecular Histology\",\"FirstCategoryId\":\"99\",\"ListUrlMain\":\"https://link.springer.com/article/10.1007/s10735-024-10256-8\",\"RegionNum\":4,\"RegionCategory\":\"生物学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"CELL BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Molecular Histology","FirstCategoryId":"99","ListUrlMain":"https://link.springer.com/article/10.1007/s10735-024-10256-8","RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"CELL BIOLOGY","Score":null,"Total":0}
tsRNA-3043a intensifies apoptosis and senescence of ovarian granulosa cells to drive premature ovarian failure by targeting FLT1
Premature ovarian failure (POF) represents the pathological aging of the ovary. The tRNA-derived small fragments (tsRNAs) play significant roles in diseases; however, whether tsRNAs are involved in POF remains unknown. The cell and mice models of POF were established, and the tsRNAs profile in the ovarian tissues of POF mice was revealed through sequencing. The functions of tsRNA-3043a and its target gene FLT1 in POF cells and mice were detected. POF mice were characterized by a decreased number of normal follicles, ovarian weight, SOD level, and serum contents of E2, LH, and FSH. A total of 81 tsRNAs were aberrantly expressed in the ovarian tissue of POF mice. The expression of tsRNA-3043a was up-regulated in POF mice. tsRNA-3043a mimics inhibited the proliferation and promoted apoptosis, lipid accumulation, and cellular senescence of ovarian granulosa KGN cells, as well as altered the transcriptome. tsRNA-3043a inhibitor had the opposite effect. tsRNA-3043a targets and binds to FLT1. Overexpression of FLT1 protected KGN cells from pathological aging. tsRNA-3043a promotes the progression of POF by inhibiting FLT1 in vitro and in vivo. tsRNA-3043a targets FLT1 and promotes apoptosis and senescence of ovarian granulosa cells, leading to the progression of POF. This study provides a new target for pharmacological intervention in POF.
期刊介绍：
The Journal of Molecular Histology publishes results of original research on the localization and expression of molecules in animal cells, tissues and organs. Coverage includes studies describing novel cellular or ultrastructural distributions of molecules which provide insight into biochemical or physiological function, development, histologic structure and disease processes.
Major research themes of particular interest include:
- Cell-Cell and Cell-Matrix Interactions;
- Connective Tissues;
- Development and Disease;
- Neuroscience.
Please note that the Journal of Molecular Histology does not consider manuscripts dealing with the application of immunological or other probes on non-standard laboratory animal models unless the results are clearly of significant and general biological importance.
The Journal of Molecular Histology publishes full-length original research papers, review articles, short communications and letters to the editors. All manuscripts are typically reviewed by two independent referees. The Journal of Molecular Histology is a continuation of The Histochemical Journal.
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