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β Common receptor integrates the erythropoietin signaling in activation of endothelial nitric oxide synthase.
J Cell Physiol. 2011 Dec; 226(12):3330-9.JC

Abstract

Erythropoietin (EPO), the key hormone for erythropoiesis, also increases nitric oxide (NO) bioavailability in endothelial cells (ECs), yet the definitive mechanisms are not fully understood. Increasing evidence has demonstrated that β common receptor (βCR) plays a crucial role in EPO-mediated non-hematopoietic effects. We investigated the role of βCR in EPO-induced endothelial NO synthase (eNOS) activation in bovine aortic ECs (BAECs) and the molecular mechanisms involved. Results of confocal microscopy and immunoprecipitation analyses revealed that βCR was colocalized and interacted with EPO receptor (EPOR) in ECs. Inhibition of βCR or EPOR by neutralizing antibodies or small interfering RNA abolished the EPO-induced NO production. Additionally, blockage of βCR abrogated the EPO-induced increase in the phosphorylation of eNOS, Akt, Src, or Janus kinase 2 (JAK2). Immunoprecipitation analysis revealed that treatment with EPO increased the interaction between βCR and eNOS, which was suppressed by inhibition of Src, JAK2, or Akt signaling with specific pharmacological inhibitors. Furthermore, EPO-induced EC proliferation, migration, and tube formation were blocked by pretreatment with βCR antibody and Src, JAK2, or PI3K/Akt inhibitors. Moreover, in vivo experiments showed that EPO increased the level of phosphorylated eNOS, Src, JAK2, and Akt, as well as βCR-eNOS association in aortas and promoted the angiogenesis in Matrigel plug, which was diminished by βCR or EPOR neutralizing antibodies. Our findings suggest that βCR may play an integrative role in the EPO signaling-mediated activation of eNOS in ECs.

Authors+Show Affiliations

Department of Physiology, National Yang-Ming University, Taipei, Taiwan.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

21321940

Citation

Su, Kuo-Hui, et al. "Β Common Receptor Integrates the Erythropoietin Signaling in Activation of Endothelial Nitric Oxide Synthase." Journal of Cellular Physiology, vol. 226, no. 12, 2011, pp. 3330-9.
Su KH, Shyue SK, Kou YR, et al. Β Common receptor integrates the erythropoietin signaling in activation of endothelial nitric oxide synthase. J Cell Physiol. 2011;226(12):3330-9.
Su, K. H., Shyue, S. K., Kou, Y. R., Ching, L. C., Chiang, A. N., Yu, Y. B., Chen, C. Y., Pan, C. C., & Lee, T. S. (2011). Β Common receptor integrates the erythropoietin signaling in activation of endothelial nitric oxide synthase. Journal of Cellular Physiology, 226(12), 3330-9. https://doi.org/10.1002/jcp.22678
Su KH, et al. Β Common Receptor Integrates the Erythropoietin Signaling in Activation of Endothelial Nitric Oxide Synthase. J Cell Physiol. 2011;226(12):3330-9. PubMed PMID: 21321940.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - β Common receptor integrates the erythropoietin signaling in activation of endothelial nitric oxide synthase. AU - Su,Kuo-Hui, AU - Shyue,Song-Kun, AU - Kou,Yu Ru, AU - Ching,Li-Chieh, AU - Chiang,An-Na, AU - Yu,Yuan-Bin, AU - Chen,Chien-Yu, AU - Pan,Ching-Chian, AU - Lee,Tzong-Shyuan, PY - 2011/2/16/entrez PY - 2011/2/16/pubmed PY - 2011/11/15/medline SP - 3330 EP - 9 JF - Journal of cellular physiology JO - J. Cell. Physiol. VL - 226 IS - 12 N2 - Erythropoietin (EPO), the key hormone for erythropoiesis, also increases nitric oxide (NO) bioavailability in endothelial cells (ECs), yet the definitive mechanisms are not fully understood. Increasing evidence has demonstrated that β common receptor (βCR) plays a crucial role in EPO-mediated non-hematopoietic effects. We investigated the role of βCR in EPO-induced endothelial NO synthase (eNOS) activation in bovine aortic ECs (BAECs) and the molecular mechanisms involved. Results of confocal microscopy and immunoprecipitation analyses revealed that βCR was colocalized and interacted with EPO receptor (EPOR) in ECs. Inhibition of βCR or EPOR by neutralizing antibodies or small interfering RNA abolished the EPO-induced NO production. Additionally, blockage of βCR abrogated the EPO-induced increase in the phosphorylation of eNOS, Akt, Src, or Janus kinase 2 (JAK2). Immunoprecipitation analysis revealed that treatment with EPO increased the interaction between βCR and eNOS, which was suppressed by inhibition of Src, JAK2, or Akt signaling with specific pharmacological inhibitors. Furthermore, EPO-induced EC proliferation, migration, and tube formation were blocked by pretreatment with βCR antibody and Src, JAK2, or PI3K/Akt inhibitors. Moreover, in vivo experiments showed that EPO increased the level of phosphorylated eNOS, Src, JAK2, and Akt, as well as βCR-eNOS association in aortas and promoted the angiogenesis in Matrigel plug, which was diminished by βCR or EPOR neutralizing antibodies. Our findings suggest that βCR may play an integrative role in the EPO signaling-mediated activation of eNOS in ECs. SN - 1097-4652 UR - https://www.unboundmedicine.com/medline/citation/21321940/β_Common_receptor_integrates_the_erythropoietin_signaling_in_activation_of_endothelial_nitric_oxide_synthase_ L2 - https://doi.org/10.1002/jcp.22678 DB - PRIME DP - Unbound Medicine ER -