NDLI: Synergistic upregulation of erythropoietin receptor (EPO-R) expression by sense and antisense EPO-R transcripts in the canine lung

Content Provider	PubMed Central
Author	Zhang, Quiyang Zhang, Jianning Moe, Orson W. Hsia, Connie C. W.
Abstract	We previously found increased erythropoietin receptor (EPO-R) protein levels in vigorously growing canine lungs after pneumonectomy (PNX), suggesting a role for paracrine EPO signaling in lung growth and remodeling. Now we find that sense and antisense EPO-R transcripts (sEPO-R and asEPO-R, respectively) are concordantly up-regulated in the post-PNX remaining lung, leading to the hypothesis that sEPO-R and asEPO-R interactions enhance EPO signaling during lung growth. We cloned a canine asEPO-R cDNA, which is fully complementary to the sense strand of the EPO-R gene from 2.5kb 3′ to the sense stop codon, and extends into the 5′ UTR of the sEPO-R transcript. Both asEPO-R and sEPO-R transcripts colocalize with EPO-R protein in the same lung cells. In cultured human embryonic kidney (HEK293) cells, transfection with sEPO-R (+FLAG tag) cDNA alone increased EPO-R protein expression (anti-EPO-R and anti-FLAG). At constant sEPO-R cDNA levels, cotransfection with escalating asEPO-R cDNA further increased recombinant EPO-R protein expression. The asEPO-R transcript harbors two putative opening reading frames (ORFs). Separate transfection of each asEPO-R ORF cDNA resulted in differential stimulatory effects on EPO-R protein expression. We conclude that both sEPO-R and asEPO-R transcripts contribute to in vivo up-regulation of EPO-R protein expression in the post-PNX remaining lung. This demonstrates synergism between sense–antisense EPO-R transcripts in response to physiological stimulation in a robust model of induced lung growth.
Related Links	http://dx.doi.org/10.1073/pnas.0802467105
Starting Page	7612
File Format	PDF
ISSN	10916490
e-ISSN	10916490
Journal	Proceedings of the National Academy of Sciences of the United States of America
Issue Number	21
Volume Number	105
Language	English
Publisher	National Academy of Sciences
Publisher Date	2008-05-27
Access Restriction	Open
Rights Holder	National Academy of Sciences
Subject Keyword	Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

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