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睫状神经营养因子(CNTF)通过JAK2-STAT3途径调节胶原蛋白表达,从而导致盆腔器官脱垂。

Ciliary neurotrophic factor (CNTF) contributes to pelvic organ prolapse by modulating collagen expression via the JAK2-STAT3 pathway.

作者信息

Xu Zhonglei, Zhu Qiyin, Yang Ying, Shan Wenjun, Jiang Fang, Zou Qianli, Wang Wenyan

机构信息

The Second Affiliated Hospital of Anhui Medical University, Hefei, 230601, People's Republic of China.

School of Pharmacy, Anhui Medical University, Hefei, 230032, People's Republic of China.

出版信息

J Mol Histol. 2025 Mar 14;56(2):107. doi: 10.1007/s10735-025-10383-w.

DOI:10.1007/s10735-025-10383-w
PMID:40082289
Abstract

Pelvic organ prolapse (POP) is a prevalent condition that affects postmenopausal women and significantly impacts their quality of life. The most common potential causes include vaginal delivery, age, and obesity. However, the specific pathophysiological mechanisms involved remain unclear. Therefore, we conducted a comparative analysis of vaginal anterior wall-associated proteins between POP patients and non-POP patients using Masson staining, immunohistochemistry, western blotting, and real-time quantitative fluorescence PCR. Additionally, we investigated the effect of ciliary neurotrophic factor (CNTF) on collagen secretion by fibroblasts in cell culture and instantaneous transfection experiments. Furthermore, the role of CNTF in the development of POP was investigated by constructing a rat prolapse model in which bilateral ovaries were removed and vaginal delivery was simulated. The findings indicated that the anterior vaginal wall of POP patients exhibited high CNTF expression, low collagen I expression, and high collagen III expression. Furthermore, cell transfection experiments demonstrated that CNTF may inhibit collagen I expression and promote collagen III expression by activating the JAK2-STAT3 pathway. A rat model constructed by simulating vaginal delivery after bilateral ovary removal is also an appropriate animal model for studying POP.

摘要

盆腔器官脱垂(POP)是一种常见病症,影响绝经后女性,并对其生活质量产生重大影响。最常见的潜在病因包括阴道分娩、年龄和肥胖。然而,其中具体的病理生理机制仍不清楚。因此,我们使用Masson染色、免疫组织化学、蛋白质印迹法和实时定量荧光PCR对POP患者和非POP患者的阴道前壁相关蛋白进行了比较分析。此外,我们在细胞培养和瞬时转染实验中研究了睫状神经营养因子(CNTF)对成纤维细胞胶原蛋白分泌的影响。此外,通过构建双侧卵巢切除并模拟阴道分娩的大鼠脱垂模型,研究了CNTF在POP发生发展中的作用。研究结果表明,POP患者的阴道前壁表现出CNTF高表达、I型胶原蛋白低表达和III型胶原蛋白高表达。此外,细胞转染实验表明,CNTF可能通过激活JAK2-STAT3通路抑制I型胶原蛋白表达并促进III型胶原蛋白表达。双侧卵巢切除后模拟阴道分娩构建的大鼠模型也是研究POP的合适动物模型。

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本文引用的文献

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Expression of insulin-like growth factor binding protein 5 in the vaginal wall tissues of older women with pelvic organ prolapse.胰岛素样生长因子结合蛋白 5 在老年盆腔器官脱垂患者阴道壁组织中的表达。
Sci Rep. 2024 Aug 7;14(1):18353. doi: 10.1038/s41598-024-69098-9.
2
Race/Ethnicity and Incidence of Pelvic Organ Prolapse in Midlife Women: The Study of Women's Health Across the Nation.种族/民族与中年女性盆腔器官脱垂的发生率:全美女性健康研究。
J Womens Health (Larchmt). 2024 Aug;33(8):1042-1051. doi: 10.1089/jwh.2023.0804. Epub 2024 Mar 29.
3
The difference in extracellular matrix metabolism in women with and without pelvic organ prolapse: A systematic review and meta-analysis.
患有和不患有盆腔器官脱垂的女性细胞外基质代谢的差异:系统评价和荟萃分析。
BJOG. 2024 Jul;131(8):1029-1041. doi: 10.1111/1471-0528.17768. Epub 2024 Jan 31.
4
Pelvic floor injury during vaginal birth is life-altering and preventable: what can we do about it?阴道分娩期间的盆底损伤会改变生活且可预防:对此我们能做些什么?
Am J Obstet Gynecol. 2024 Mar;230(3):279-294.e2. doi: 10.1016/j.ajog.2023.11.1253. Epub 2024 Jan 2.
5
Estrogen inhibits the differentiation of fibroblasts induced by high stiffness matrix by enhancing DNMT1 expression.雌激素通过增强 DNMT1 表达抑制高刚性基质诱导的成纤维细胞分化。
Tissue Cell. 2023 Dec;85:102207. doi: 10.1016/j.tice.2023.102207. Epub 2023 Sep 1.
6
Ovariectomy with simulated vaginal delivery to establish a rat model for pelvic organ prolapse.卵巢切除术伴模拟阴道分娩建立大鼠盆腔器官脱垂模型
Connect Tissue Res. 2023 Jul;64(4):376-388. doi: 10.1080/03008207.2023.2199091. Epub 2023 Apr 24.
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Regeneration and functional recovery of the completely transected optic nerve in adult rats by CNTF-chitosan.睫状神经营养因子-壳聚糖促进成年大鼠完全横断视神经的再生及功能恢复
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Prevalence of pelvic floor disorders in adult women being seen in a primary care setting and associated risk factors.成年女性在初级保健机构就诊时盆底疾病的流行情况及相关危险因素。
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