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The RXFP2-PLC/PKC signaling pathway mediates INSL3-induced regulation of the proliferation, migration and apoptosis of mouse gubernacular cells

BACKGROUND: Testicular hypoplasia can affect the sexual and reproductive ability in adulthood, and even increase the risk of cancer. Abnormal development of the gubernaculum is one of the important factors of testicular hypoplasia. Therefore, a study of the structure and function of the gubernaculum...

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Autores principales: Duan, Shouxing, Jiang, Xuewu, Li, Jianhong, Fu, Maxian, Li, Zhuo, Cheng, Yiyi, Zhuang, Yangmu, Yang, Ming, Xiao, Wenfeng, Ping, Hongyan, Xie, Yao, Xie, Xiaojun, Zhang, Xuan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9972740/
https://www.ncbi.nlm.nih.gov/pubmed/36849880
http://dx.doi.org/10.1186/s11658-023-00433-0
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author Duan, Shouxing
Jiang, Xuewu
Li, Jianhong
Fu, Maxian
Li, Zhuo
Cheng, Yiyi
Zhuang, Yangmu
Yang, Ming
Xiao, Wenfeng
Ping, Hongyan
Xie, Yao
Xie, Xiaojun
Zhang, Xuan
author_facet Duan, Shouxing
Jiang, Xuewu
Li, Jianhong
Fu, Maxian
Li, Zhuo
Cheng, Yiyi
Zhuang, Yangmu
Yang, Ming
Xiao, Wenfeng
Ping, Hongyan
Xie, Yao
Xie, Xiaojun
Zhang, Xuan
author_sort Duan, Shouxing
collection PubMed
description BACKGROUND: Testicular hypoplasia can affect the sexual and reproductive ability in adulthood, and even increase the risk of cancer. Abnormal development of the gubernaculum is one of the important factors of testicular hypoplasia. Therefore, a study of the structure and function of the gubernaculum is an important but neglected new breakthrough point for investigating the normal/abnormal development of the testis. Previous findings showed that Insulin like factor 3 (INSL3) is a key factor regulating the growth of gubernaculum, however, the mechanism by which INSL3 acts on the gubernaculum remains unknown. Therefore, we probed the mechanism associated with INSL3-induced the proliferation, migration, and apoptosis of gubernacular cells in mice. METHODS: A culture cell model of neonatal mice gubernaculum is established by INSL3 intervention. We blocked PLC/PKC signaling pathway with U73122 pretreat to investigate the role of the PLC/PKC signaling pathway. The changes of cell proliferation, migration, and apoptosis were detected by molecular biological methods. In addition, the levels of PCNA and F-action were detected by immunofluorescence and western blotting. RESULTS: We found that INSL3 can promote the proliferation and migration of gubernacular cells and inhibit their apoptosis, meanwhile, INSL3 significantly up-regulated PLC/PKC protein phosphorylation. However, treatment with the PLC/PKC signaling pathway inhibitor U73122 significantly inhibited these effects of INSL3. Besides, we found that INSL3 could up-regulate the protein expression level of PCNA and F-actin, while the PCNA and F-actin expression was significantly weakened after U73122 pretreatment. CONCLUSIONS: This research revealed that INSL3 binding to RXFP2 may up-regulate the expression levels of PCNA and F-actin by activating the PLC/PKC signaling pathway to promote the proliferation and migration of gubernacular cells. It suggests that the RXFP2-PLC/PKC axis may serve as a novel molecular mechanism by which INSL3 regulates growth of the gubernaculum. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s11658-023-00433-0.
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spelling pubmed-99727402023-03-01 The RXFP2-PLC/PKC signaling pathway mediates INSL3-induced regulation of the proliferation, migration and apoptosis of mouse gubernacular cells Duan, Shouxing Jiang, Xuewu Li, Jianhong Fu, Maxian Li, Zhuo Cheng, Yiyi Zhuang, Yangmu Yang, Ming Xiao, Wenfeng Ping, Hongyan Xie, Yao Xie, Xiaojun Zhang, Xuan Cell Mol Biol Lett Research Letter BACKGROUND: Testicular hypoplasia can affect the sexual and reproductive ability in adulthood, and even increase the risk of cancer. Abnormal development of the gubernaculum is one of the important factors of testicular hypoplasia. Therefore, a study of the structure and function of the gubernaculum is an important but neglected new breakthrough point for investigating the normal/abnormal development of the testis. Previous findings showed that Insulin like factor 3 (INSL3) is a key factor regulating the growth of gubernaculum, however, the mechanism by which INSL3 acts on the gubernaculum remains unknown. Therefore, we probed the mechanism associated with INSL3-induced the proliferation, migration, and apoptosis of gubernacular cells in mice. METHODS: A culture cell model of neonatal mice gubernaculum is established by INSL3 intervention. We blocked PLC/PKC signaling pathway with U73122 pretreat to investigate the role of the PLC/PKC signaling pathway. The changes of cell proliferation, migration, and apoptosis were detected by molecular biological methods. In addition, the levels of PCNA and F-action were detected by immunofluorescence and western blotting. RESULTS: We found that INSL3 can promote the proliferation and migration of gubernacular cells and inhibit their apoptosis, meanwhile, INSL3 significantly up-regulated PLC/PKC protein phosphorylation. However, treatment with the PLC/PKC signaling pathway inhibitor U73122 significantly inhibited these effects of INSL3. Besides, we found that INSL3 could up-regulate the protein expression level of PCNA and F-actin, while the PCNA and F-actin expression was significantly weakened after U73122 pretreatment. CONCLUSIONS: This research revealed that INSL3 binding to RXFP2 may up-regulate the expression levels of PCNA and F-actin by activating the PLC/PKC signaling pathway to promote the proliferation and migration of gubernacular cells. It suggests that the RXFP2-PLC/PKC axis may serve as a novel molecular mechanism by which INSL3 regulates growth of the gubernaculum. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s11658-023-00433-0. BioMed Central 2023-02-27 /pmc/articles/PMC9972740/ /pubmed/36849880 http://dx.doi.org/10.1186/s11658-023-00433-0 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Research Letter
Duan, Shouxing
Jiang, Xuewu
Li, Jianhong
Fu, Maxian
Li, Zhuo
Cheng, Yiyi
Zhuang, Yangmu
Yang, Ming
Xiao, Wenfeng
Ping, Hongyan
Xie, Yao
Xie, Xiaojun
Zhang, Xuan
The RXFP2-PLC/PKC signaling pathway mediates INSL3-induced regulation of the proliferation, migration and apoptosis of mouse gubernacular cells
title The RXFP2-PLC/PKC signaling pathway mediates INSL3-induced regulation of the proliferation, migration and apoptosis of mouse gubernacular cells
title_full The RXFP2-PLC/PKC signaling pathway mediates INSL3-induced regulation of the proliferation, migration and apoptosis of mouse gubernacular cells
title_fullStr The RXFP2-PLC/PKC signaling pathway mediates INSL3-induced regulation of the proliferation, migration and apoptosis of mouse gubernacular cells
title_full_unstemmed The RXFP2-PLC/PKC signaling pathway mediates INSL3-induced regulation of the proliferation, migration and apoptosis of mouse gubernacular cells
title_short The RXFP2-PLC/PKC signaling pathway mediates INSL3-induced regulation of the proliferation, migration and apoptosis of mouse gubernacular cells
title_sort rxfp2-plc/pkc signaling pathway mediates insl3-induced regulation of the proliferation, migration and apoptosis of mouse gubernacular cells
topic Research Letter
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9972740/
https://www.ncbi.nlm.nih.gov/pubmed/36849880
http://dx.doi.org/10.1186/s11658-023-00433-0
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