Cyanidin-3-O-Glucoside Rescues Zearalenone-Induced Apoptosis via the ITGA7-PI3K-AKT Signaling Pathway in Porcine Ovarian Granulosa Cells
Zearalenone (ZEN) is an important secondary metabolite of <i>Fusarium fungi</i>, exposure to which can cause reproductive disorders through its effects on ovarian granulosa cells (GCs) in many mammals, especially in pigs. This study aimed to investigate the protective effects of Cyanidin...
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MDPI AG
2023-02-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/24/5/4441 |
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| author | Xiuxiu Li Jingya Wang Fali Zhang Mubin Yu Ning Zuo Lan Li Jinghe Tan Wei Shen |
| author_facet | Xiuxiu Li Jingya Wang Fali Zhang Mubin Yu Ning Zuo Lan Li Jinghe Tan Wei Shen |
| author_sort | Xiuxiu Li |
| collection | DOAJ |
| description | Zearalenone (ZEN) is an important secondary metabolite of <i>Fusarium fungi</i>, exposure to which can cause reproductive disorders through its effects on ovarian granulosa cells (GCs) in many mammals, especially in pigs. This study aimed to investigate the protective effects of Cyanidin-3-O-glucoside (C3G) on the ZEN-induced negative effects in porcine GCs (pGCs). The pGCs were treated with 30 µM ZEN and/or 20 µM C3G for 24 h; they were divided into a control (Ctrl) group, ZEN group, ZEN+C3G (Z+C) group, and a C3G group. Bioinformatics analysis was used to systematically screen differentially expressed genes (DEGs) in the rescue process. Results showed that C3G could effectively rescue ZEN-induced apoptosis in pGCs, and notably increase cell viability and proliferation. Furthermore, 116 DEGs were identified, and the phosphatidylinositide 3-kinases-protein kinase B (PI3K-AKT) signaling pathway was the center of attention, of which five genes and the PI3K-AKT signaling pathway were confirmed by real-time quantitative PCR (qPCR) and/or Western blot (WB). As analyzed, ZEN inhibited mRNA and protein levels of integrin subunit alpha-7 (ITGA7), and promoted the expression of cell cycle inhibition kinase cyclin-D3 (<i>CCND3</i>) and cyclin-dependent kinase inhibitor 1 (<i>CDKN1A</i>). After the knock-down of <i>ITGA7</i> by siRNA, the PI3K-AKT signaling pathway was significantly inhibited. Meanwhile, proliferating cell nuclear antigen (PCNA) expression decreased, and apoptosis rates and pro-apoptotic proteins increased. In conclusion, our study demonstrated that C3G exhibited significant protective effects on the ZEN-induced inhibition of proliferation and apoptosis via the ITGA7-PI3K-AKT pathway. |
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| spelling | doaj.art-33104f5755ec413aa1036dcc970eaf812023-11-17T07:48:40ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-02-01245444110.3390/ijms24054441Cyanidin-3-O-Glucoside Rescues Zearalenone-Induced Apoptosis via the ITGA7-PI3K-AKT Signaling Pathway in Porcine Ovarian Granulosa CellsXiuxiu Li0Jingya Wang1Fali Zhang2Mubin Yu3Ning Zuo4Lan Li5Jinghe Tan6Wei Shen7College of Animal Science and Veterinary Medicine, Shandong Agricultural University, Tai’an 271018, ChinaCollege of Life Sciences, Qingdao Agricultural University, Qingdao 266109, ChinaCollege of Animal Science and Veterinary Medicine, Shandong Agricultural University, Tai’an 271018, ChinaCollege of Life Sciences, Qingdao Agricultural University, Qingdao 266109, ChinaCollege of Life Sciences, Qingdao Agricultural University, Qingdao 266109, ChinaCollege of Life Sciences, Qingdao Agricultural University, Qingdao 266109, ChinaCollege of Animal Science and Veterinary Medicine, Shandong Agricultural University, Tai’an 271018, ChinaCollege of Animal Science and Veterinary Medicine, Shandong Agricultural University, Tai’an 271018, ChinaZearalenone (ZEN) is an important secondary metabolite of <i>Fusarium fungi</i>, exposure to which can cause reproductive disorders through its effects on ovarian granulosa cells (GCs) in many mammals, especially in pigs. This study aimed to investigate the protective effects of Cyanidin-3-O-glucoside (C3G) on the ZEN-induced negative effects in porcine GCs (pGCs). The pGCs were treated with 30 µM ZEN and/or 20 µM C3G for 24 h; they were divided into a control (Ctrl) group, ZEN group, ZEN+C3G (Z+C) group, and a C3G group. Bioinformatics analysis was used to systematically screen differentially expressed genes (DEGs) in the rescue process. Results showed that C3G could effectively rescue ZEN-induced apoptosis in pGCs, and notably increase cell viability and proliferation. Furthermore, 116 DEGs were identified, and the phosphatidylinositide 3-kinases-protein kinase B (PI3K-AKT) signaling pathway was the center of attention, of which five genes and the PI3K-AKT signaling pathway were confirmed by real-time quantitative PCR (qPCR) and/or Western blot (WB). As analyzed, ZEN inhibited mRNA and protein levels of integrin subunit alpha-7 (ITGA7), and promoted the expression of cell cycle inhibition kinase cyclin-D3 (<i>CCND3</i>) and cyclin-dependent kinase inhibitor 1 (<i>CDKN1A</i>). After the knock-down of <i>ITGA7</i> by siRNA, the PI3K-AKT signaling pathway was significantly inhibited. Meanwhile, proliferating cell nuclear antigen (PCNA) expression decreased, and apoptosis rates and pro-apoptotic proteins increased. In conclusion, our study demonstrated that C3G exhibited significant protective effects on the ZEN-induced inhibition of proliferation and apoptosis via the ITGA7-PI3K-AKT pathway.https://www.mdpi.com/1422-0067/24/5/4441cyanidin-3-O-glucosidezearalenoneITGA7-PI3K-AKT signaling pathwayporcine granulosa cells |
| spellingShingle | Xiuxiu Li Jingya Wang Fali Zhang Mubin Yu Ning Zuo Lan Li Jinghe Tan Wei Shen Cyanidin-3-O-Glucoside Rescues Zearalenone-Induced Apoptosis via the ITGA7-PI3K-AKT Signaling Pathway in Porcine Ovarian Granulosa Cells International Journal of Molecular Sciences cyanidin-3-O-glucoside zearalenone ITGA7-PI3K-AKT signaling pathway porcine granulosa cells |
| title | Cyanidin-3-O-Glucoside Rescues Zearalenone-Induced Apoptosis via the ITGA7-PI3K-AKT Signaling Pathway in Porcine Ovarian Granulosa Cells |
| title_full | Cyanidin-3-O-Glucoside Rescues Zearalenone-Induced Apoptosis via the ITGA7-PI3K-AKT Signaling Pathway in Porcine Ovarian Granulosa Cells |
| title_fullStr | Cyanidin-3-O-Glucoside Rescues Zearalenone-Induced Apoptosis via the ITGA7-PI3K-AKT Signaling Pathway in Porcine Ovarian Granulosa Cells |
| title_full_unstemmed | Cyanidin-3-O-Glucoside Rescues Zearalenone-Induced Apoptosis via the ITGA7-PI3K-AKT Signaling Pathway in Porcine Ovarian Granulosa Cells |
| title_short | Cyanidin-3-O-Glucoside Rescues Zearalenone-Induced Apoptosis via the ITGA7-PI3K-AKT Signaling Pathway in Porcine Ovarian Granulosa Cells |
| title_sort | cyanidin 3 o glucoside rescues zearalenone induced apoptosis via the itga7 pi3k akt signaling pathway in porcine ovarian granulosa cells |
| topic | cyanidin-3-O-glucoside zearalenone ITGA7-PI3K-AKT signaling pathway porcine granulosa cells |
| url | https://www.mdpi.com/1422-0067/24/5/4441 |
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