tsRNA-3043a intensifies apoptosis and senescence of ovarian granulosa cells to drive premature ovarian failure by targeting FLT1

IF 2.9 4区生物学 Q3 CELL BIOLOGY

Journal of Molecular Histology Pub Date : 2024-09-30 DOI:10.1007/s10735-024-10256-8

Jianzhen Huang, Fang Zeng, Hongxia Yi, Lixia Wan, Qinggang Xu

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引用次数: 0

Abstract

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.

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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。

卵巢早衰（POF）代表着卵巢的病理性衰老。tRNA衍生的小片段（tsRNAs）在疾病中发挥着重要作用，但tsRNAs是否参与了POF仍是未知数。我们建立了 POF 的细胞和小鼠模型，并通过测序揭示了 POF 小鼠卵巢组织中 tsRNAs 的特征。检测了 tsRNA-3043a 及其靶基因 FLT1 在 POF 细胞和小鼠中的功能。POF小鼠的特征是正常卵泡数量、卵巢重量、SOD水平以及血清中E2、LH和FSH含量下降。共有 81 个 tsRNA 在 POF 小鼠的卵巢组织中异常表达。tsRNA-3043a模拟物抑制卵巢颗粒KGN细胞的增殖，促进其凋亡、脂质积累和细胞衰老，并改变其转录组。过表达 FLT1 可保护 KGN 细胞免于病理衰老。tsRNA-3043a 通过在体外和体内抑制 FLT1 促进 POF 的进展。这项研究为药物干预 POF 提供了一个新靶点。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Journal of Molecular Histology 生物-细胞生物学

CiteScore

5.90

自引率

0.00%

发文量

审稿时长

1 months

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.