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下调 TASK-3 通道诱导牛囊性卵巢卵泡颗粒细胞衰老。

Downregulation of TASK-3 Channel Induces Senescence in Granulosa Cells of Bovine Cystic Ovarian Follicles.

机构信息

Department of Obstetrics and Gynecology, Samsung Changwon Hospital, Sungkyunkwan University School of Medicine, Changwon 51353, Republic of Korea.

Department of Physiology, Institute of Medical Sciences, College of Medicine, Gyeongsang National University, Jinju 52727, Republic of Korea.

出版信息

Int J Mol Sci. 2024 Sep 23;25(18):10199. doi: 10.3390/ijms251810199.

DOI:10.3390/ijms251810199
PMID:39337686
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11432027/
Abstract

Ovarian cysts are linked to hormone imbalances and altered gene expressions, but the connection between cysts and ion channel expression is understudied. This study explored the role of TWIK-related acid-sensitive K (TASK) channels in bovine ovarian cyst formation. The ovarian follicles were split into small (5 to 10 mm in diameter) and large (>25 mm in diameter) groups. Among the measured K, Na, and Cl concentrations in follicular fluid (FF) obtained from small-sized follicles (SFs) and large-sized follicles (LFs), the K concentration was significantly lower in LFFF. Quantitative PCR, Western blot, and immunocytochemistry data revealed that TASK-3 expression levels significantly decreased by approximately 50% in LFs and granulosa cells obtained from LFs (LFGCs) compared to the corresponding controls. The TASK-3 protein was localized to the plasma membranes of GCs. The diameters of LFGCs were larger than those of SFGCs. The cell swelling response to exposure to a hypotonic solution (200 mOsm/L) was highly reduced in TASK-3-overexpressing cells compared to vector-transfected cells. TASK-3-knockdown cells showed arrested growth. Senescence markers were detected in LFGCs and TASK-3-knockdown cells. These findings suggest that reduced TASK-3 expression in LFs is associated with the inhibition of GC growth, leading to senescence and cyst formation.

摘要

卵巢囊肿与激素失衡和基因表达改变有关,但囊肿与离子通道表达之间的联系还研究得不够充分。本研究探讨了 TWIK 相关酸敏感 K(TASK)通道在牛卵巢囊肿形成中的作用。将卵巢卵泡分为小卵泡(直径 5 至 10 毫米)和大卵泡(直径大于 25 毫米)两组。在从小卵泡(SF)和大卵泡(LF)获得的卵泡液(FF)中测量的 K、Na 和 Cl 浓度中,LFFF 中的 K 浓度显著降低。定量 PCR、Western blot 和免疫细胞化学数据显示,与相应对照相比,TASK-3 在 LF 和 LF 来源的颗粒细胞(LFGCs)中的表达水平显著降低了约 50%。TASK-3 蛋白定位于 GC 的质膜上。LFGC 的直径大于 SFGC。与转染载体的细胞相比,暴露于低渗溶液(200 mOsm/L)时 TASK-3 过表达细胞的细胞肿胀反应高度降低。TASK-3 敲低细胞的生长停滞。在 LFGC 和 TASK-3 敲低细胞中检测到衰老标志物。这些发现表明,LF 中 TASK-3 表达的减少与 GC 生长的抑制有关,导致衰老和囊肿形成。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b588/11432027/3c2839c27d89/ijms-25-10199-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b588/11432027/224895744d6a/ijms-25-10199-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b588/11432027/13d030f613a8/ijms-25-10199-g002.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b588/11432027/3c2839c27d89/ijms-25-10199-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b588/11432027/224895744d6a/ijms-25-10199-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b588/11432027/13d030f613a8/ijms-25-10199-g002.jpg
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