GDNF enhances HGF-induced tubulogenesis and organization of Sertoli cell.

IF 3.2 3区医学 Q2 GENETICS & HEREDITY

Journal of Assisted Reproduction and Genetics Pub Date : 2025-06-01 Epub Date: 2025-05-22 DOI:10.1007/s10815-025-03493-7

Begum Durkut-Kuzu, Ciler Celik-Ozenci

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引用次数: 0

Abstract

Purpose: Hepatocyte growth factor (HGF), secreted by Sertoli cells, activates the c-Met receptor, facilitating seminiferous tubule formation. Glial cell-derived neurotrophic factor (GDNF) promotes embryonic Sertoli cell proliferation and cord formation. This study aimed to investigate whether exogenous GDNF contributes to HGF-induced in vitro organization of Sertoli cells in a Matrigel-based three-dimensional (3D) culture system.

Methods: Four experimental groups were established using the 15P-1 Sertoli cell line: control, HGF-treated, GDNF-treated, and combined HGF- and GDNF-treated. Tubular structure length and branching were quantified using image analysis software, while the expression of ZO-1 protein was assessed via immunofluorescence staining in 3D Matrigel-based culture for 5 days. Additionally, Gfrα-1, Ret, Ncam, and Met mRNA expression in Sertoli cells were analyzed. The expression levels of ZO-1, c-MET, and p-c-MET were analyzed in two-dimensional (2D) culture after 5 days.

Results: Quantitative analysis revealed a significant increase in the length and branching of tubular-like structures when GDNF was co-administered with HGF, compared to other groups. Additionally, there was a notable increase in ZO-1 protein expression with the combined administration of GDNF and HGF, surpassing levels observed in the control group. Furthermore, co-administration of HGF and GDNF significantly elevated phospho-c-Met levels compared to the control group.

Conclusion: Our study reveals that exogenous GDNF enhances the HGF-induced tubular organization of Sertoli cells in vitro. The concurrent administration of GDNF and HGF markedly augments the formation of tubular structures and the expression of the ZO-1 protein, indicating a potential synergistic influence on the organizational and signaling cascades within Sertoli cells.

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GDNF促进hgf诱导的小管形成和支持细胞的组织。

目的：肝细胞生长因子（HGF）由支持细胞分泌，激活c-Met受体，促进精小管的形成。神经胶质细胞源性神经营养因子（GDNF）促进胚胎支持细胞增殖和脊髓形成。本研究旨在探讨外源性GDNF是否有助于hgf诱导的体外基质三维（3D）培养系统中支持细胞的组织。方法：以15P-1 Sertoli细胞系为实验对象，分别建立对照组、HGF处理组、gdnf处理组、HGF + gdnf联合处理组。用图像分析软件定量分析管状结构长度和分支，用免疫荧光染色法检测ZO-1蛋白在3D基质培养5天后的表达。同时分析Gfrα-1、Ret、Ncam和Met mRNA在Sertoli细胞中的表达。5天后，在二维（2D）培养中分析ZO-1、c-MET和p-c-MET的表达水平。结果：定量分析显示，与其他组相比，GDNF与HGF共给药时，管状结构的长度和分支明显增加。此外，在GDNF和HGF联合给药的情况下，ZO-1蛋白表达显著增加，超过对照组。此外，与对照组相比，HGF和GDNF联合施用显著提高了磷酸c- met水平。结论：我们的研究表明外源性GDNF增强了hgf诱导的体外支持细胞的管状组织。同时给药GDNF和HGF显著增加了管状结构的形成和ZO-1蛋白的表达，表明对支持细胞内的组织和信号级联具有潜在的协同影响。

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 Assisted Reproduction and Genetics 医学-妇产科学

CiteScore

5.70

自引率

9.70%

发文量

286

审稿时长

1 months

期刊介绍： The Journal of Assisted Reproduction and Genetics publishes cellular, molecular, genetic, and epigenetic discoveries advancing our understanding of the biology and underlying mechanisms from gametogenesis to offspring health. Special emphasis is placed on the practice and evolution of assisted reproduction technologies (ARTs) with reference to the diagnosis and management of diseases affecting fertility. Our goal is to educate our readership in the translation of basic and clinical discoveries made from human or relevant animal models to the safe and efficacious practice of human ARTs. The scientific rigor and ethical standards embraced by the JARG editorial team ensures a broad international base of expertise guiding the marriage of contemporary clinical research paradigms with basic science discovery. JARG publishes original papers, minireviews, case reports, and opinion pieces often combined into special topic issues that will educate clinicians and scientists with interests in the mechanisms of human development that bear on the treatment of infertility and emerging innovations in human ARTs. The guiding principles of male and female reproductive health impacting pre- and post-conceptional viability and developmental potential are emphasized within the purview of human reproductive health in current and future generations of our species. The journal is published in cooperation with the American Society for Reproductive Medicine, an organization of more than 8,000 physicians, researchers, nurses, technicians and other professionals dedicated to advancing knowledge and expertise in reproductive biology.