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Am J Physiol Regul Integr Comp Physiol. 2012 Sep 15;303(6):R665-75. doi: 10.1152/ajpregu.00478.2011. Epub 2012 Aug 1.

Acute regulation of activin A and its binding protein, follistatin, in serum and tissues following lipopolysaccharide treatment of adult male mice.

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1
Monash Institute of Medical Research, Monash University, Melbourne, Victoria, Australia. hui.wu@monash.edu

Abstract

Activin A, a member of the transforming growth factor-β family, increases in the circulation within 1 h after administration of bacterial LPS. To clarify the origins of this rapid increase, the distribution of activin A and its binding protein, follistatin, and their production following LPS treatment, were assessed in adult male mice. In untreated mice, activin A was detectable in all 23 tissues examined, with highest mRNA expression (as measured by quantitative RT-PCR) was found in the liver, and the largest concentration of activin A protein (by ELISA) was found in the bone marrow. Likewise, follistatin mRNA and protein were present in all tissues, with highest expression in the vas deferens. Activin A and follistatin mRNA did not increase significantly in any tissue within the first hour after LPS, but activin A protein decreased by 35% in the bone marrow and increased 5-fold in the lung. No significant changes were observed in any other tissue. Activin A reached a peak in the circulation 1 h following LPS, and then declined. Cycloheximide, an inhibitor of protein translation, reduced this increase of activin A by more than 50%. Actinomycin D, an inhibitor of mRNA transcription, had no effect. Circulating follistatin did not increase until 4 h after LPS and was not affected by either inhibitor. These data indicate that the rapid increase in circulating activin A during LPS-induced inflammation is regulated at the posttranscriptional level, apparently from newly translated and stored protein, and implicate bone marrow-derived cells, and, in particular, neutrophils, as a significant source of this preformed activin A.

PMID:
22855279
DOI:
10.1152/ajpregu.00478.2011
[Indexed for MEDLINE]
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