KLF13 Regulates the Activity of the GH-Induced JAK/STAT Signaling by Targeting Genes Involved in the Pathway
The Krüppel-like factor 13 (KLF13) has emerged as an important transcription factor involved in essential processes of the central nervous system (CNS). It predominantly functions as a transcriptional repressor, impacting the activity of several signaling pathways with essential roles in the CNS, in...
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2023-07-01
|
| Series: | International Journal of Molecular Sciences |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1422-0067/24/13/11187 |
| _version_ | 1797591487486099456 |
|---|---|
| author | José Ávila-Mendoza Karen Delgado-Rueda Valeria A. Urban-Sosa Martha Carranza Maricela Luna Carlos G. Martínez-Moreno Carlos Arámburo |
| author_facet | José Ávila-Mendoza Karen Delgado-Rueda Valeria A. Urban-Sosa Martha Carranza Maricela Luna Carlos G. Martínez-Moreno Carlos Arámburo |
| author_sort | José Ávila-Mendoza |
| collection | DOAJ |
| description | The Krüppel-like factor 13 (KLF13) has emerged as an important transcription factor involved in essential processes of the central nervous system (CNS). It predominantly functions as a transcriptional repressor, impacting the activity of several signaling pathways with essential roles in the CNS, including the JAK/STAT pathway, which is the canonical mediator of growth hormone (GH) signaling. It is now recognized that GH has important actions as a neurotrophic factor. Therefore, we analyzed the effects of KLF13 on the activity of the JAK/STAT signaling pathway in the hippocampus-derived cell line HT22. Results showed that KLF13 directly regulates the expression of several genes involved in the JAK-STAT pathway, including <i>Jak1</i>, <i>Jak2</i>, Jak3, and <i>Socs1</i>, by associating with their proximal gene promoters. In addition, it was found that in KLF13-deficient HT22 neurons, the expression of <i>Jak1</i>, <i>Stat3</i>, <i>Socs1</i>, <i>Socs3</i>, and <i>Igf1</i> was dysregulated, exhibiting mRNA levels that went up to 7-fold higher than the control cell line. KLF13 displayed a differential effect on the GH-induced JAK/STAT pathway activity, decreasing the STAT3 branch while enhancing the STAT5 branch. In KLF13-deficient HT22 cells, the activity of the STAT3 branch was enhanced, mediating the GH-dependent augmented expression of the JAK/STAT output genes <i>Socs1</i>, <i>Socs3</i>, <i>Igf1</i>, and <i>Bdnf</i>. Furthermore, GH treatment increased both the nuclear content of KLF13 and <i>Klf13</i> mRNA levels, suggesting that KLF13 could be part of the mechanisms that maintain the homeostatic state of this pathway. These findings support the notion that KLF13 is a regulator of JAK/STAT activity. |
| first_indexed | 2024-03-11T01:38:07Z |
| format | Article |
| id | doaj.art-71e0c837038d40309578e419c9c27618 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-11T01:38:07Z |
| publishDate | 2023-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-71e0c837038d40309578e419c9c276182023-11-18T16:49:24ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-07-0124131118710.3390/ijms241311187KLF13 Regulates the Activity of the GH-Induced JAK/STAT Signaling by Targeting Genes Involved in the PathwayJosé Ávila-Mendoza0Karen Delgado-Rueda1Valeria A. Urban-Sosa2Martha Carranza3Maricela Luna4Carlos G. Martínez-Moreno5Carlos Arámburo6Departamento de Neurobiología Celular y Molecular, Instituto de Neurobiología, Campus Juriquilla, Universidad Nacional Autónoma de México, Querétaro 76230, MexicoDepartamento de Neurobiología Celular y Molecular, Instituto de Neurobiología, Campus Juriquilla, Universidad Nacional Autónoma de México, Querétaro 76230, MexicoDepartamento de Neurobiología Celular y Molecular, Instituto de Neurobiología, Campus Juriquilla, Universidad Nacional Autónoma de México, Querétaro 76230, MexicoDepartamento de Neurobiología Celular y Molecular, Instituto de Neurobiología, Campus Juriquilla, Universidad Nacional Autónoma de México, Querétaro 76230, MexicoDepartamento de Neurobiología Celular y Molecular, Instituto de Neurobiología, Campus Juriquilla, Universidad Nacional Autónoma de México, Querétaro 76230, MexicoDepartamento de Neurobiología Celular y Molecular, Instituto de Neurobiología, Campus Juriquilla, Universidad Nacional Autónoma de México, Querétaro 76230, MexicoDepartamento de Neurobiología Celular y Molecular, Instituto de Neurobiología, Campus Juriquilla, Universidad Nacional Autónoma de México, Querétaro 76230, MexicoThe Krüppel-like factor 13 (KLF13) has emerged as an important transcription factor involved in essential processes of the central nervous system (CNS). It predominantly functions as a transcriptional repressor, impacting the activity of several signaling pathways with essential roles in the CNS, including the JAK/STAT pathway, which is the canonical mediator of growth hormone (GH) signaling. It is now recognized that GH has important actions as a neurotrophic factor. Therefore, we analyzed the effects of KLF13 on the activity of the JAK/STAT signaling pathway in the hippocampus-derived cell line HT22. Results showed that KLF13 directly regulates the expression of several genes involved in the JAK-STAT pathway, including <i>Jak1</i>, <i>Jak2</i>, Jak3, and <i>Socs1</i>, by associating with their proximal gene promoters. In addition, it was found that in KLF13-deficient HT22 neurons, the expression of <i>Jak1</i>, <i>Stat3</i>, <i>Socs1</i>, <i>Socs3</i>, and <i>Igf1</i> was dysregulated, exhibiting mRNA levels that went up to 7-fold higher than the control cell line. KLF13 displayed a differential effect on the GH-induced JAK/STAT pathway activity, decreasing the STAT3 branch while enhancing the STAT5 branch. In KLF13-deficient HT22 cells, the activity of the STAT3 branch was enhanced, mediating the GH-dependent augmented expression of the JAK/STAT output genes <i>Socs1</i>, <i>Socs3</i>, <i>Igf1</i>, and <i>Bdnf</i>. Furthermore, GH treatment increased both the nuclear content of KLF13 and <i>Klf13</i> mRNA levels, suggesting that KLF13 could be part of the mechanisms that maintain the homeostatic state of this pathway. These findings support the notion that KLF13 is a regulator of JAK/STAT activity.https://www.mdpi.com/1422-0067/24/13/11187Krüppel-like factorsJAK/STATgrowth hormonehippocampal neuronssignal transduction |
| spellingShingle | José Ávila-Mendoza Karen Delgado-Rueda Valeria A. Urban-Sosa Martha Carranza Maricela Luna Carlos G. Martínez-Moreno Carlos Arámburo KLF13 Regulates the Activity of the GH-Induced JAK/STAT Signaling by Targeting Genes Involved in the Pathway International Journal of Molecular Sciences Krüppel-like factors JAK/STAT growth hormone hippocampal neurons signal transduction |
| title | KLF13 Regulates the Activity of the GH-Induced JAK/STAT Signaling by Targeting Genes Involved in the Pathway |
| title_full | KLF13 Regulates the Activity of the GH-Induced JAK/STAT Signaling by Targeting Genes Involved in the Pathway |
| title_fullStr | KLF13 Regulates the Activity of the GH-Induced JAK/STAT Signaling by Targeting Genes Involved in the Pathway |
| title_full_unstemmed | KLF13 Regulates the Activity of the GH-Induced JAK/STAT Signaling by Targeting Genes Involved in the Pathway |
| title_short | KLF13 Regulates the Activity of the GH-Induced JAK/STAT Signaling by Targeting Genes Involved in the Pathway |
| title_sort | klf13 regulates the activity of the gh induced jak stat signaling by targeting genes involved in the pathway |
| topic | Krüppel-like factors JAK/STAT growth hormone hippocampal neurons signal transduction |
| url | https://www.mdpi.com/1422-0067/24/13/11187 |
| work_keys_str_mv | AT joseavilamendoza klf13regulatestheactivityoftheghinducedjakstatsignalingbytargetinggenesinvolvedinthepathway AT karendelgadorueda klf13regulatestheactivityoftheghinducedjakstatsignalingbytargetinggenesinvolvedinthepathway AT valeriaaurbansosa klf13regulatestheactivityoftheghinducedjakstatsignalingbytargetinggenesinvolvedinthepathway AT marthacarranza klf13regulatestheactivityoftheghinducedjakstatsignalingbytargetinggenesinvolvedinthepathway AT maricelaluna klf13regulatestheactivityoftheghinducedjakstatsignalingbytargetinggenesinvolvedinthepathway AT carlosgmartinezmoreno klf13regulatestheactivityoftheghinducedjakstatsignalingbytargetinggenesinvolvedinthepathway AT carlosaramburo klf13regulatestheactivityoftheghinducedjakstatsignalingbytargetinggenesinvolvedinthepathway |