Protective effect of silencing Stat1 on high glucose-induced podocytes injury via Forkhead transcription factor O1-regulated the oxidative stress response
Abstract Background Podocyte plays an important role in maintaining the integrity and function of the glomerular filtration barrier. Various studies reported that forkhead transcription factor (Fox) O1 played a key role in anti-oxidative signaling. This study aimed to investigate the role of Stat1 i...
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| Format: | Article |
| Language: | English |
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BMC
2019-07-01
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| Series: | BMC Molecular and Cell Biology |
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| Online Access: | http://link.springer.com/article/10.1186/s12860-019-0209-0 |
| _version_ | 1818151068395110400 |
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| author | Hongkun Wang Yanhui Zhang Fangfang Xia Wei Zhang Peng Chen Guoan Yang |
| author_facet | Hongkun Wang Yanhui Zhang Fangfang Xia Wei Zhang Peng Chen Guoan Yang |
| author_sort | Hongkun Wang |
| collection | DOAJ |
| description | Abstract Background Podocyte plays an important role in maintaining the integrity and function of the glomerular filtration barrier. Various studies reported that forkhead transcription factor (Fox) O1 played a key role in anti-oxidative signaling. This study aimed to investigate the role of Stat1 in high glucose (HG) -induced podocyte injury. Methods Under normal glucose, hypertonic and HG stimulated podocyte conditions, cell counting kit-8 (CCK-8) assay, flow cytometry and western blot and quantitative real-time polymerase chain reaction (qRT-PCR) were respectively carried out to determine cell viability, apoptosis, reactive oxygen species (ROS) production and related genes expressions. We then respectively used silent Stat1, simultaneous silencing Stat1 and FoxO1 and over-expression of FoxO1, to observe whether they/it could reverse the damage of podocytes induced by HG. Results High glucose attenuated cell survival and promoted cell apoptosis in MPC-5 cells at the same time, and it was also observed to promote the protein expression of Stat1 and the FoxO1 expression inhibition. Silencing Stat1 could reverse HG-induced podocytes injury. Specifically, siStat1 increased cell viability, inhibited cell apoptosis and attenuated ROS level in a high-glucose environment. Cleaved caspase-3 and pro-apoptosis protein Bax was significantly down-regulated, and anti-apoptosis protein Bcl-2 was up-regulated by siStat1. The antioxidant genes Catalase, MnSOD, NQO1 and HO1 were up-regulated by siStat1. We found that silencing FoxO1 reversed the protective effect of siStat1 on the HG-induced podocytes injury. Conclusions Silencing Stat1 could reverse the effects of high glucose-triggered low cell viability, cell apoptosis and ROS release and the functions of Stat1 might be involved in FoxO1 mediated-oxidative stress in nucleus. |
| first_indexed | 2024-12-11T13:32:57Z |
| format | Article |
| id | doaj.art-826c5c9ebd5146b599d52f740353e664 |
| institution | Directory Open Access Journal |
| issn | 2661-8850 |
| language | English |
| last_indexed | 2024-12-11T13:32:57Z |
| publishDate | 2019-07-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Molecular and Cell Biology |
| spelling | doaj.art-826c5c9ebd5146b599d52f740353e6642022-12-22T01:05:11ZengBMCBMC Molecular and Cell Biology2661-88502019-07-0120111510.1186/s12860-019-0209-0Protective effect of silencing Stat1 on high glucose-induced podocytes injury via Forkhead transcription factor O1-regulated the oxidative stress responseHongkun Wang0Yanhui Zhang1Fangfang Xia2Wei Zhang3Peng Chen4Guoan Yang5Department of Nephrology, The First Affiliated Hospital of Baotou Medical College Inner Mongolia University of Science and TechnologyDepartment of Nephrology, The First Affiliated Hospital of Baotou Medical College Inner Mongolia University of Science and TechnologyDepartment of Nephrology, North HospitalCentral Laboratory, The First Affiliated Hospital of Baotou Medical College Inner Mongolia University of Science and TechnologyDepartment of Nutriology, The First Affiliated Hospital of Baotou Medical College Inner Mongolia University of Science and TechnologyCentral Laboratory, The First Affiliated Hospital of Baotou Medical College Inner Mongolia University of Science and TechnologyAbstract Background Podocyte plays an important role in maintaining the integrity and function of the glomerular filtration barrier. Various studies reported that forkhead transcription factor (Fox) O1 played a key role in anti-oxidative signaling. This study aimed to investigate the role of Stat1 in high glucose (HG) -induced podocyte injury. Methods Under normal glucose, hypertonic and HG stimulated podocyte conditions, cell counting kit-8 (CCK-8) assay, flow cytometry and western blot and quantitative real-time polymerase chain reaction (qRT-PCR) were respectively carried out to determine cell viability, apoptosis, reactive oxygen species (ROS) production and related genes expressions. We then respectively used silent Stat1, simultaneous silencing Stat1 and FoxO1 and over-expression of FoxO1, to observe whether they/it could reverse the damage of podocytes induced by HG. Results High glucose attenuated cell survival and promoted cell apoptosis in MPC-5 cells at the same time, and it was also observed to promote the protein expression of Stat1 and the FoxO1 expression inhibition. Silencing Stat1 could reverse HG-induced podocytes injury. Specifically, siStat1 increased cell viability, inhibited cell apoptosis and attenuated ROS level in a high-glucose environment. Cleaved caspase-3 and pro-apoptosis protein Bax was significantly down-regulated, and anti-apoptosis protein Bcl-2 was up-regulated by siStat1. The antioxidant genes Catalase, MnSOD, NQO1 and HO1 were up-regulated by siStat1. We found that silencing FoxO1 reversed the protective effect of siStat1 on the HG-induced podocytes injury. Conclusions Silencing Stat1 could reverse the effects of high glucose-triggered low cell viability, cell apoptosis and ROS release and the functions of Stat1 might be involved in FoxO1 mediated-oxidative stress in nucleus.http://link.springer.com/article/10.1186/s12860-019-0209-0Stat1FoxO1PodocyteHGOxidative stress |
| spellingShingle | Hongkun Wang Yanhui Zhang Fangfang Xia Wei Zhang Peng Chen Guoan Yang Protective effect of silencing Stat1 on high glucose-induced podocytes injury via Forkhead transcription factor O1-regulated the oxidative stress response BMC Molecular and Cell Biology Stat1 FoxO1 Podocyte HG Oxidative stress |
| title | Protective effect of silencing Stat1 on high glucose-induced podocytes injury via Forkhead transcription factor O1-regulated the oxidative stress response |
| title_full | Protective effect of silencing Stat1 on high glucose-induced podocytes injury via Forkhead transcription factor O1-regulated the oxidative stress response |
| title_fullStr | Protective effect of silencing Stat1 on high glucose-induced podocytes injury via Forkhead transcription factor O1-regulated the oxidative stress response |
| title_full_unstemmed | Protective effect of silencing Stat1 on high glucose-induced podocytes injury via Forkhead transcription factor O1-regulated the oxidative stress response |
| title_short | Protective effect of silencing Stat1 on high glucose-induced podocytes injury via Forkhead transcription factor O1-regulated the oxidative stress response |
| title_sort | protective effect of silencing stat1 on high glucose induced podocytes injury via forkhead transcription factor o1 regulated the oxidative stress response |
| topic | Stat1 FoxO1 Podocyte HG Oxidative stress |
| url | http://link.springer.com/article/10.1186/s12860-019-0209-0 |
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