TGF-β1-Mediated Activation of SERPINE1 is Involved in Hemin-Induced Apoptotic and Inflammatory Injury in HT22 Cells
Tinggang Wang,1,* Haibin Lu,2,* Deqiang Li,2 Weichun Huang3 1Emergency Department, Affiliated Hospital of Zunyi Medical University, Zunyi, People’s Republic of China; 2Department of Critical Care Medicine, Daping Hospital, Army Medical University, Chongqing, People’s Republic of...
Guardado en:
| Autores principales: | , , , |
|---|---|
| Formato: | article |
| Lenguaje: | EN |
| Publicado: |
Dove Medical Press
2021
|
| Materias: | |
| Acceso en línea: | https://doaj.org/article/a6486a7de442475384cc13a755d6a526 |
| Etiquetas: |
Agregar Etiqueta
Sin Etiquetas, Sea el primero en etiquetar este registro!
|
| id |
oai:doaj.org-article:a6486a7de442475384cc13a755d6a526 |
|---|---|
| record_format |
dspace |
| spelling |
oai:doaj.org-article:a6486a7de442475384cc13a755d6a5262021-12-02T14:24:09ZTGF-β1-Mediated Activation of SERPINE1 is Involved in Hemin-Induced Apoptotic and Inflammatory Injury in HT22 Cells1178-2021https://doaj.org/article/a6486a7de442475384cc13a755d6a5262021-02-01T00:00:00Zhttps://www.dovepress.com/tgf-beta1-mediated-activation-of-serpine1-is-involved-in-hemin-induced-peer-reviewed-article-NDThttps://doaj.org/toc/1178-2021Tinggang Wang,1,* Haibin Lu,2,* Deqiang Li,2 Weichun Huang3 1Emergency Department, Affiliated Hospital of Zunyi Medical University, Zunyi, People’s Republic of China; 2Department of Critical Care Medicine, Daping Hospital, Army Medical University, Chongqing, People’s Republic of China; 3Radiology Department, First Affiliated Hospital of Army Medical University, Chongqing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Weichun HuangRadiology Department, First Affiliated Hospital of Army Medical University, No. 30, Gao Tan Yan Main Street, Shapingba District, Chongqing, 400038, People’s Republic of ChinaTel +86-023-68754425Email weichun_huang@163.comBackground: Intracerebral hemorrhage (ICH) is a severe subtype of stroke with high mortality and morbidity. Serpin Family E Member 1 (SERPINE1) has been documented to be upregulated following ICH, however, the participation of SERPINE1 in the development of ICH has never been studied.Methods: Hemin was utilized to develop an in vitro model of ICH. Gene levels were evaluated by the use of quantitative reverse transcription polymerase chain reaction, Western blot, as well as enzyme-linked immunoassay assay. The activity of caspase-3 was determined using a commercial kit. Cell viability and apoptosis were assessed using 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and Terminal deoxynucleotidyl transferase (TdT) d UTP Nick-End Labeling assay.Results: SERPINE1 was upregulated in hemin-treated HT22 cells. Silencing of SERPINE1 attenuated hemin-induced inhibition of cell viability. Moreover, knockdown of SERPINE1 repressed hemin-induced apoptosis in HT22 cells, as evidenced by the decrease in the number of TUNEL positive cells, caspase-3 activity, and Bax expression, and the increase in Bcl-2 expression. Meanwhile, knockdown of SERPINE1 repressed hemin-induced inflammation in HT22 cells, as indicated by reduced levels of tumor necrosis factor-α, interleukin-6 (IL-6), IL-1β, and inducible nitric oxide synthase. We also found that transforming growth factor-beta 1 (TGF-β 1) induced SERPINE1 expression in a dose-dependent manner. Besides, SERPINE1 knockdown attenuated the effects of TGF-β 1 on hemin-induced neuronal damage.Conclusion: TGF-β 1-induced SERPINE1 activation exacerbated hemin-induced apoptosis and inflammation in HT22 cells, manifesting a novel mechanism for ICH progression.Keywords: intracerebral hemorrhage, serpin family E member 1, transforming growth factor-beta 1Wang TLu HLi DHuang WDove Medical Pressarticleintracerebral hemorrhageserpin family e member 1transforming growth factor-beta 1 Neurosciences. Biological psychiatry. NeuropsychiatryRC321-571Neurology. Diseases of the nervous systemRC346-429ENNeuropsychiatric Disease and Treatment, Vol Volume 17, Pp 423-433 (2021) |
| institution |
DOAJ |
| collection |
DOAJ |
| language |
EN |
| topic |
intracerebral hemorrhage serpin family e member 1 transforming growth factor-beta 1 Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571 Neurology. Diseases of the nervous system RC346-429 |
| spellingShingle |
intracerebral hemorrhage serpin family e member 1 transforming growth factor-beta 1 Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571 Neurology. Diseases of the nervous system RC346-429 Wang T Lu H Li D Huang W TGF-β1-Mediated Activation of SERPINE1 is Involved in Hemin-Induced Apoptotic and Inflammatory Injury in HT22 Cells |
| description |
Tinggang Wang,1,* Haibin Lu,2,* Deqiang Li,2 Weichun Huang3 1Emergency Department, Affiliated Hospital of Zunyi Medical University, Zunyi, People’s Republic of China; 2Department of Critical Care Medicine, Daping Hospital, Army Medical University, Chongqing, People’s Republic of China; 3Radiology Department, First Affiliated Hospital of Army Medical University, Chongqing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Weichun HuangRadiology Department, First Affiliated Hospital of Army Medical University, No. 30, Gao Tan Yan Main Street, Shapingba District, Chongqing, 400038, People’s Republic of ChinaTel +86-023-68754425Email weichun_huang@163.comBackground: Intracerebral hemorrhage (ICH) is a severe subtype of stroke with high mortality and morbidity. Serpin Family E Member 1 (SERPINE1) has been documented to be upregulated following ICH, however, the participation of SERPINE1 in the development of ICH has never been studied.Methods: Hemin was utilized to develop an in vitro model of ICH. Gene levels were evaluated by the use of quantitative reverse transcription polymerase chain reaction, Western blot, as well as enzyme-linked immunoassay assay. The activity of caspase-3 was determined using a commercial kit. Cell viability and apoptosis were assessed using 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and Terminal deoxynucleotidyl transferase (TdT) d UTP Nick-End Labeling assay.Results: SERPINE1 was upregulated in hemin-treated HT22 cells. Silencing of SERPINE1 attenuated hemin-induced inhibition of cell viability. Moreover, knockdown of SERPINE1 repressed hemin-induced apoptosis in HT22 cells, as evidenced by the decrease in the number of TUNEL positive cells, caspase-3 activity, and Bax expression, and the increase in Bcl-2 expression. Meanwhile, knockdown of SERPINE1 repressed hemin-induced inflammation in HT22 cells, as indicated by reduced levels of tumor necrosis factor-α, interleukin-6 (IL-6), IL-1β, and inducible nitric oxide synthase. We also found that transforming growth factor-beta 1 (TGF-β 1) induced SERPINE1 expression in a dose-dependent manner. Besides, SERPINE1 knockdown attenuated the effects of TGF-β 1 on hemin-induced neuronal damage.Conclusion: TGF-β 1-induced SERPINE1 activation exacerbated hemin-induced apoptosis and inflammation in HT22 cells, manifesting a novel mechanism for ICH progression.Keywords: intracerebral hemorrhage, serpin family E member 1, transforming growth factor-beta 1 |
| format |
article |
| author |
Wang T Lu H Li D Huang W |
| author_facet |
Wang T Lu H Li D Huang W |
| author_sort |
Wang T |
| title |
TGF-β1-Mediated Activation of SERPINE1 is Involved in Hemin-Induced Apoptotic and Inflammatory Injury in HT22 Cells |
| title_short |
TGF-β1-Mediated Activation of SERPINE1 is Involved in Hemin-Induced Apoptotic and Inflammatory Injury in HT22 Cells |
| title_full |
TGF-β1-Mediated Activation of SERPINE1 is Involved in Hemin-Induced Apoptotic and Inflammatory Injury in HT22 Cells |
| title_fullStr |
TGF-β1-Mediated Activation of SERPINE1 is Involved in Hemin-Induced Apoptotic and Inflammatory Injury in HT22 Cells |
| title_full_unstemmed |
TGF-β1-Mediated Activation of SERPINE1 is Involved in Hemin-Induced Apoptotic and Inflammatory Injury in HT22 Cells |
| title_sort |
tgf-β1-mediated activation of serpine1 is involved in hemin-induced apoptotic and inflammatory injury in ht22 cells |
| publisher |
Dove Medical Press |
| publishDate |
2021 |
| url |
https://doaj.org/article/a6486a7de442475384cc13a755d6a526 |
| work_keys_str_mv |
AT wangt tgfbeta1mediatedactivationofserpine1isinvolvedinhemininducedapoptoticandinflammatoryinjuryinht22cells AT luh tgfbeta1mediatedactivationofserpine1isinvolvedinhemininducedapoptoticandinflammatoryinjuryinht22cells AT lid tgfbeta1mediatedactivationofserpine1isinvolvedinhemininducedapoptoticandinflammatoryinjuryinht22cells AT huangw tgfbeta1mediatedactivationofserpine1isinvolvedinhemininducedapoptoticandinflammatoryinjuryinht22cells |
| _version_ |
1718391443214565376 |