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Cathepsin B Regulates Mice Granulosa Cells’ Apoptosis and Proliferation In Vitro
Cathepsin B (CTSB), a lysosomal cysteine protease’s high expression and activity, has been reported to cause poor-quality embryos in porcine and bovine. Nevertheless, CTSB functions in mice granulosa cells remain to explore. To discuss the CTSB functional role in follicular dynamics, we studied apop...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8584394/ https://www.ncbi.nlm.nih.gov/pubmed/34769258 http://dx.doi.org/10.3390/ijms222111827 |
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author | Chen, Chao Ahmad, Muhammad Jamil Ye, Tingzhu Du, Chao Zhang, Xinxin Liang, Aixin Yang, Liguo |
author_facet | Chen, Chao Ahmad, Muhammad Jamil Ye, Tingzhu Du, Chao Zhang, Xinxin Liang, Aixin Yang, Liguo |
author_sort | Chen, Chao |
collection | PubMed |
description | Cathepsin B (CTSB), a lysosomal cysteine protease’s high expression and activity, has been reported to cause poor-quality embryos in porcine and bovine. Nevertheless, CTSB functions in mice granulosa cells remain to explore. To discuss the CTSB functional role in follicular dynamics, we studied apoptosis, proliferation, cell cycle progression, and related signaling pathways in primary mouse granulosa cells transfected with small interference RNA specific to CTSB (siCTSB) for 48 h. Further, mRNA and protein expression of cell proliferation regulators (Myc and cyclin D2), apoptosis regulators (caspase 3, caspase 8, TNF-α, and Bcl2), steroidogenesis-related genes (FSHR and CYP11A1), and autophagy markers (LC3-I and ATG5) were investigated. In addition, the effect of CTSB on steroidogenesis and autophagy was also examined. Flow cytometry analysis assay displayed that silencing of CTSB decreased the early and total apoptosis rate by downregulating TNF-α, caspase 8, and caspase 3, and upregulating Bcl2. By regulating Myc and cyclin D2 expression and activating the p-Akt and p-ERK pathways, CTSB knockdown increased GC proliferation and number. A significant decline in estradiol and progesterone concentrations was observed parallel to a significant decrease in autophagy-related markers LC3-I and ATG5 compared to the control group. Herein, we demonstrated that CTSB serves as a proapoptotic agent and plays a critical role in folliculogenesis in female mice by mediating apoptosis, autophagy, proliferation, and steroidogenesis. Hence, CTSB could be a potential prognostic agent for female infertility. |
format | Online Article Text |
id | pubmed-8584394 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-85843942021-11-12 Cathepsin B Regulates Mice Granulosa Cells’ Apoptosis and Proliferation In Vitro Chen, Chao Ahmad, Muhammad Jamil Ye, Tingzhu Du, Chao Zhang, Xinxin Liang, Aixin Yang, Liguo Int J Mol Sci Article Cathepsin B (CTSB), a lysosomal cysteine protease’s high expression and activity, has been reported to cause poor-quality embryos in porcine and bovine. Nevertheless, CTSB functions in mice granulosa cells remain to explore. To discuss the CTSB functional role in follicular dynamics, we studied apoptosis, proliferation, cell cycle progression, and related signaling pathways in primary mouse granulosa cells transfected with small interference RNA specific to CTSB (siCTSB) for 48 h. Further, mRNA and protein expression of cell proliferation regulators (Myc and cyclin D2), apoptosis regulators (caspase 3, caspase 8, TNF-α, and Bcl2), steroidogenesis-related genes (FSHR and CYP11A1), and autophagy markers (LC3-I and ATG5) were investigated. In addition, the effect of CTSB on steroidogenesis and autophagy was also examined. Flow cytometry analysis assay displayed that silencing of CTSB decreased the early and total apoptosis rate by downregulating TNF-α, caspase 8, and caspase 3, and upregulating Bcl2. By regulating Myc and cyclin D2 expression and activating the p-Akt and p-ERK pathways, CTSB knockdown increased GC proliferation and number. A significant decline in estradiol and progesterone concentrations was observed parallel to a significant decrease in autophagy-related markers LC3-I and ATG5 compared to the control group. Herein, we demonstrated that CTSB serves as a proapoptotic agent and plays a critical role in folliculogenesis in female mice by mediating apoptosis, autophagy, proliferation, and steroidogenesis. Hence, CTSB could be a potential prognostic agent for female infertility. MDPI 2021-10-31 /pmc/articles/PMC8584394/ /pubmed/34769258 http://dx.doi.org/10.3390/ijms222111827 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Chen, Chao Ahmad, Muhammad Jamil Ye, Tingzhu Du, Chao Zhang, Xinxin Liang, Aixin Yang, Liguo Cathepsin B Regulates Mice Granulosa Cells’ Apoptosis and Proliferation In Vitro |
title | Cathepsin B Regulates Mice Granulosa Cells’ Apoptosis and Proliferation In Vitro |
title_full | Cathepsin B Regulates Mice Granulosa Cells’ Apoptosis and Proliferation In Vitro |
title_fullStr | Cathepsin B Regulates Mice Granulosa Cells’ Apoptosis and Proliferation In Vitro |
title_full_unstemmed | Cathepsin B Regulates Mice Granulosa Cells’ Apoptosis and Proliferation In Vitro |
title_short | Cathepsin B Regulates Mice Granulosa Cells’ Apoptosis and Proliferation In Vitro |
title_sort | cathepsin b regulates mice granulosa cells’ apoptosis and proliferation in vitro |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8584394/ https://www.ncbi.nlm.nih.gov/pubmed/34769258 http://dx.doi.org/10.3390/ijms222111827 |
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