Modulation of cellular stress response via the erythropoietin/CD131 heteroreceptor complex in mouse mesenchymal-derived cells
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| 024 | 7 | 0 | |a 10.1007/s00109-014-1218-2 |2 doi |
| 035 | |a (NATIONALLICENCE)springer-10.1007/s00109-014-1218-2 | ||
| 245 | 0 | 0 | |a Modulation of cellular stress response via the erythropoietin/CD131 heteroreceptor complex in mouse mesenchymal-derived cells |h [Elektronische Daten] |c [Stefan Bohr, Suraj Patel, Radovan Vasko, Keyue Shen, Arvin Iracheta-Vellve, Jungwoo Lee, Shyam Bale, Nilay Chakraborty, Michael Brines, Anthony Cerami, Francois Berthiaume, Martin Yarmush] |
| 520 | 3 | |a Tissue-protective properties of erythropoietin (EPO) have let to the discovery of an alternative EPO signaling via an EPO-R/CD131 receptor complex which can now be specifically targeted through pharmaceutically designed short sequence peptides such as ARA290. However, little is still known about specific functions of alternative EPO signaling in defined cell populations. In this study, we investigated effects of signaling through EPO-R/CD131 complex on cellular stress responses and pro-inflammatory activation in different mesenchymal-derived phenotypes. We show that anti-apoptotic, anti-inflammatory effects of ARA290 and EPO coincide with the externalization of CD131 receptor component as an immediate response to cellular stress. In addition, alternative EPO signaling strongly modulated transcriptional, translational, or metabolic responses after stressor removal. Specifically, we saw that ARA290 was able to overcome a TNFα-mediated inhibition of transcription factor activation related to cell stress responses, most notably of serum response factor (SRF), heat shock transcription factor protein 1 (HSF1), and activator protein 1 (AP1). We conclude that alternative EPO signaling acts as a modulator of pro-inflammatory signaling pathways and likely plays a role in restoring tissue homeostasis. Key message: • Erythropoietin (EPO) triggers an alternative pathway via heteroreceptor EPO/CD131. • ARA290 peptide specifically binds EPO/CD131 but not the canonical EPO/EPO receptor. • Oxidative stress and inflammation promote cell surface expression of CD131. • ARA290 prevents tumor necrosis factor-mediated inhibition of stress-related genes. • Alternative EPO signaling modulates inflammation and promotes tissue homeostasis. | |
| 540 | |a Springer-Verlag Berlin Heidelberg, 2014 | ||
| 690 | 7 | |a ARA290 |2 nationallicence | |
| 690 | 7 | |a Oxidative stress |2 nationallicence | |
| 690 | 7 | |a Heat shock |2 nationallicence | |
| 690 | 7 | |a Apoptosis |2 nationallicence | |
| 690 | 7 | |a TNFα |2 nationallicence | |
| 690 | 7 | |a Homeostasis |2 nationallicence | |
| 690 | 7 | |a Mesenchymal stem cells |2 nationallicence | |
| 700 | 1 | |a Bohr |D Stefan |u Center for Engineering in Medicine/Surgical Services, Massachusetts General Hospital, Harvard Medical School, and Shriners Hospitals for Children, 51 Blossom Street, 4th Floor, 02114, Boston, MA, USA |4 aut | |
| 700 | 1 | |a Patel |D Suraj |u Center for Engineering in Medicine/Surgical Services, Massachusetts General Hospital, Harvard Medical School, and Shriners Hospitals for Children, 51 Blossom Street, 4th Floor, 02114, Boston, MA, USA |4 aut | |
| 700 | 1 | |a Vasko |D Radovan |u Department of Medicine, New York Medical College, Valhalla, NY, USA |4 aut | |
| 700 | 1 | |a Shen |D Keyue |u Center for Engineering in Medicine/Surgical Services, Massachusetts General Hospital, Harvard Medical School, and Shriners Hospitals for Children, 51 Blossom Street, 4th Floor, 02114, Boston, MA, USA |4 aut | |
| 700 | 1 | |a Iracheta-Vellve |D Arvin |u Center for Engineering in Medicine/Surgical Services, Massachusetts General Hospital, Harvard Medical School, and Shriners Hospitals for Children, 51 Blossom Street, 4th Floor, 02114, Boston, MA, USA |4 aut | |
| 700 | 1 | |a Lee |D Jungwoo |u Center for Engineering in Medicine/Surgical Services, Massachusetts General Hospital, Harvard Medical School, and Shriners Hospitals for Children, 51 Blossom Street, 4th Floor, 02114, Boston, MA, USA |4 aut | |
| 700 | 1 | |a Bale |D Shyam |u Center for Engineering in Medicine/Surgical Services, Massachusetts General Hospital, Harvard Medical School, and Shriners Hospitals for Children, 51 Blossom Street, 4th Floor, 02114, Boston, MA, USA |4 aut | |
| 700 | 1 | |a Chakraborty |D Nilay |u Center for Engineering in Medicine/Surgical Services, Massachusetts General Hospital, Harvard Medical School, and Shriners Hospitals for Children, 51 Blossom Street, 4th Floor, 02114, Boston, MA, USA |4 aut | |
| 700 | 1 | |a Brines |D Michael |u Araim Pharmaceuticals, 10562, Ossining, NY, USA |4 aut | |
| 700 | 1 | |a Cerami |D Anthony |u Araim Pharmaceuticals, 10562, Ossining, NY, USA |4 aut | |
| 700 | 1 | |a Berthiaume |D Francois |u Department of Biomedical Engineering, Rutgers University, 599 Taylor Road, 08854, Piscataway, NJ, USA |4 aut | |
| 700 | 1 | |a Yarmush |D Martin |u Center for Engineering in Medicine/Surgical Services, Massachusetts General Hospital, Harvard Medical School, and Shriners Hospitals for Children, 51 Blossom Street, 4th Floor, 02114, Boston, MA, USA |4 aut | |
| 773 | 0 | |t Journal of Molecular Medicine |d Springer Berlin Heidelberg |g 93/2(2015-02-01), 199-210 |x 0946-2716 |q 93:2<199 |1 2015 |2 93 |o 109 | |
| 856 | 4 | 0 | |u https://doi.org/10.1007/s00109-014-1218-2 |q text/html |z Onlinezugriff via DOI |
| 898 | |a BK010053 |b XK010053 |c XK010000 | ||
| 900 | 7 | |a Metadata rights reserved |b Springer special CC-BY-NC licence |2 nationallicence | |
| 908 | |D 1 |a research-article |2 jats | ||
| 949 | |B NATIONALLICENCE |F NATIONALLICENCE |b NL-springer | ||
| 950 | |B NATIONALLICENCE |P 856 |E 40 |u https://doi.org/10.1007/s00109-014-1218-2 |q text/html |z Onlinezugriff via DOI | ||
| 950 | |B NATIONALLICENCE |P 700 |E 1- |a Bohr |D Stefan |u Center for Engineering in Medicine/Surgical Services, Massachusetts General Hospital, Harvard Medical School, and Shriners Hospitals for Children, 51 Blossom Street, 4th Floor, 02114, Boston, MA, USA |4 aut | ||
| 950 | |B NATIONALLICENCE |P 700 |E 1- |a Patel |D Suraj |u Center for Engineering in Medicine/Surgical Services, Massachusetts General Hospital, Harvard Medical School, and Shriners Hospitals for Children, 51 Blossom Street, 4th Floor, 02114, Boston, MA, USA |4 aut | ||
| 950 | |B NATIONALLICENCE |P 700 |E 1- |a Vasko |D Radovan |u Department of Medicine, New York Medical College, Valhalla, NY, USA |4 aut | ||
| 950 | |B NATIONALLICENCE |P 700 |E 1- |a Shen |D Keyue |u Center for Engineering in Medicine/Surgical Services, Massachusetts General Hospital, Harvard Medical School, and Shriners Hospitals for Children, 51 Blossom Street, 4th Floor, 02114, Boston, MA, USA |4 aut | ||
| 950 | |B NATIONALLICENCE |P 700 |E 1- |a Iracheta-Vellve |D Arvin |u Center for Engineering in Medicine/Surgical Services, Massachusetts General Hospital, Harvard Medical School, and Shriners Hospitals for Children, 51 Blossom Street, 4th Floor, 02114, Boston, MA, USA |4 aut | ||
| 950 | |B NATIONALLICENCE |P 700 |E 1- |a Lee |D Jungwoo |u Center for Engineering in Medicine/Surgical Services, Massachusetts General Hospital, Harvard Medical School, and Shriners Hospitals for Children, 51 Blossom Street, 4th Floor, 02114, Boston, MA, USA |4 aut | ||
| 950 | |B NATIONALLICENCE |P 700 |E 1- |a Bale |D Shyam |u Center for Engineering in Medicine/Surgical Services, Massachusetts General Hospital, Harvard Medical School, and Shriners Hospitals for Children, 51 Blossom Street, 4th Floor, 02114, Boston, MA, USA |4 aut | ||
| 950 | |B NATIONALLICENCE |P 700 |E 1- |a Chakraborty |D Nilay |u Center for Engineering in Medicine/Surgical Services, Massachusetts General Hospital, Harvard Medical School, and Shriners Hospitals for Children, 51 Blossom Street, 4th Floor, 02114, Boston, MA, USA |4 aut | ||
| 950 | |B NATIONALLICENCE |P 700 |E 1- |a Brines |D Michael |u Araim Pharmaceuticals, 10562, Ossining, NY, USA |4 aut | ||
| 950 | |B NATIONALLICENCE |P 700 |E 1- |a Cerami |D Anthony |u Araim Pharmaceuticals, 10562, Ossining, NY, USA |4 aut | ||
| 950 | |B NATIONALLICENCE |P 700 |E 1- |a Berthiaume |D Francois |u Department of Biomedical Engineering, Rutgers University, 599 Taylor Road, 08854, Piscataway, NJ, USA |4 aut | ||
| 950 | |B NATIONALLICENCE |P 700 |E 1- |a Yarmush |D Martin |u Center for Engineering in Medicine/Surgical Services, Massachusetts General Hospital, Harvard Medical School, and Shriners Hospitals for Children, 51 Blossom Street, 4th Floor, 02114, Boston, MA, USA |4 aut | ||
| 950 | |B NATIONALLICENCE |P 773 |E 0- |t Journal of Molecular Medicine |d Springer Berlin Heidelberg |g 93/2(2015-02-01), 199-210 |x 0946-2716 |q 93:2<199 |1 2015 |2 93 |o 109 | ||