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Blood pressure homeostasis is maintained by a P311-TGF-β axis.

Publication ,  Journal Article
Badri, KR; Yue, M; Carretero, OA; Aramgam, SL; Cao, J; Sharkady, S; Kim, GH; Taylor, GA; Byron, KL; Schuger, L
Published in: J Clin Invest
October 2013

P311 is an 8-kDa intracellular protein that is highly conserved across species and is expressed in the nervous system as well as in vascular and visceral smooth muscle cells. P311-null (P311-/-) mice display learning and memory defects, but alterations in their vasculature have not been previously described. Here we report that P311-/- mice are markedly hypotensive with accompanying defects in vascular tone and VSMC contractility. Functional abnormalities in P311-/- mice resulted from decreased total and active levels of TGF-β1, TGF-β2, and TGF-β3 that arise as a specific consequence of decreased translation. Vascular hypofunctionality was fully rescued in vitro and in vivo by exogenous TGF-β1-TGF-β3. Conversely, P311-transgenic (P311(TG)) mice had elevated levels of TGF-β1-TGF-β3 and subsequent hypertension. Consistent with findings attained in mouse models, arteries recovered from hypertensive human patients displayed increased P311 expression. Thus, we identified P311 as the first protein known to modulate TGF-β translation and the first pan-regulator of TGF-β expression under steady-state conditions. Together, our findings point to P311 as a critical blood pressure regulator and establish a potential link between P311 expression and the development of hypertensive disease.

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Published In

J Clin Invest

DOI

EISSN

1558-8238

Publication Date

October 2013

Volume

123

Issue

10

Start / End Page

4502 / 4512

Location

United States

Related Subject Headings

  • rhoA GTP-Binding Protein
  • rho GTP-Binding Proteins
  • Up-Regulation
  • Transforming Growth Factor beta
  • RNA, Messenger
  • Nerve Tissue Proteins
  • Myocytes, Smooth Muscle
  • Muscle, Smooth, Vascular
  • Muscle Contraction
  • Mice, Knockout
 

Citation

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Badri, K. R., Yue, M., Carretero, O. A., Aramgam, S. L., Cao, J., Sharkady, S., … Schuger, L. (2013). Blood pressure homeostasis is maintained by a P311-TGF-β axis. J Clin Invest, 123(10), 4502–4512. https://doi.org/10.1172/JCI69884
Badri, Kameswara Rao, Ming Yue, Oscar A. Carretero, Sree Latha Aramgam, Jun Cao, Stephen Sharkady, Gene H. Kim, Gregory A. Taylor, Kenneth L. Byron, and Lucia Schuger. “Blood pressure homeostasis is maintained by a P311-TGF-β axis.J Clin Invest 123, no. 10 (October 2013): 4502–12. https://doi.org/10.1172/JCI69884.
Badri KR, Yue M, Carretero OA, Aramgam SL, Cao J, Sharkady S, et al. Blood pressure homeostasis is maintained by a P311-TGF-β axis. J Clin Invest. 2013 Oct;123(10):4502–12.
Badri, Kameswara Rao, et al. “Blood pressure homeostasis is maintained by a P311-TGF-β axis.J Clin Invest, vol. 123, no. 10, Oct. 2013, pp. 4502–12. Pubmed, doi:10.1172/JCI69884.
Badri KR, Yue M, Carretero OA, Aramgam SL, Cao J, Sharkady S, Kim GH, Taylor GA, Byron KL, Schuger L. Blood pressure homeostasis is maintained by a P311-TGF-β axis. J Clin Invest. 2013 Oct;123(10):4502–4512.

Published In

J Clin Invest

DOI

EISSN

1558-8238

Publication Date

October 2013

Volume

123

Issue

10

Start / End Page

4502 / 4512

Location

United States

Related Subject Headings

  • rhoA GTP-Binding Protein
  • rho GTP-Binding Proteins
  • Up-Regulation
  • Transforming Growth Factor beta
  • RNA, Messenger
  • Nerve Tissue Proteins
  • Myocytes, Smooth Muscle
  • Muscle, Smooth, Vascular
  • Muscle Contraction
  • Mice, Knockout