GSBS Student Publications

Title

Modulation of cellular stress response via the erythropoietin/CD131 heteroreceptor complex in mouse mesenchymal-derived cells

Student Author(s)

Arvin Iracheta-Vellve

GSBS Program

Translational Science

UMMS Affiliation

Department of Medicine, Division of Gastroenterology

Date

11-6-2014

Document Type

Article

Disciplines

Cellular and Molecular Physiology | Genetics | Molecular Genetics

Abstract

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.

Comments

Citation: Bohr S, Patel SJ, Vasko R, Shen K, Iracheta-Vellve A, Lee J, Bale SS, Chakraborty N, Brines M, Cerami A, Berthiaume F, Yarmush ML. Modulation of cellular stress response via the erythropoietin/CD131 heteroreceptor complex in mouse mesenchymal-derived cells. J Mol Med (Berl). 2014 Nov 6. [Epub ahead of print]. doi:10.1007/s00109-014-1218-2

At the time of publication, Arvin Iracheta-Vellve was not yet affiliated with the University of Massachusetts Medical School.

Related Resources

Link to article in PubMed

Journal Title

Journal of molecular medicine (Berlin, Germany)

PubMed ID

25373867