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Localization of cells producing erythropoietin in murine liver by in situ
hybridization [see comments]
ST Koury, MC Bondurant, MJ Koury and GL Semenza
Veterans Affairs, Medical Center, Nashville, TN.
In situ hybridization using antisense RNA probes was used to localize cells
that produce erythropoietin (EPO) in the livers of anemic transgenic mice
expressing the human EPO gene and in livers of anemic nontransgenic mice.
In transgenic mice bled from a hematocrit of 55% to one of 10%, hepatocytes
surrounding central veins synthesized large amounts of human EPO mRNA.
EPO-producing cells were very rare in the area of portal triads. In
transgenic mice bled to a hematocrit of 20%, a similar number and
distribution of cells contained human EPO mRNA as was found with a 10%
hematocrit, but the cells were less heavily labeled, indicating increased
EPO production per cell at 10% hematocrit as compared with 20% hematocrit.
No human EPO mRNA was detected in the kidneys of anemic transgenic mice,
although endogenous murine EPO mRNA was strongly expressed in cortical
interstitial cells. In sections of livers from nontransgenic mice bled from
a hematocrit of 45% to one of 10%, only isolated cells produced EPO. When
the types of cells could clearly be identified, approximately 80% of these
cells were hepatocytes, while 20% had a nonepithelial morphology and were
located in or adjacent to the sinusoidal spaces. When the sense strand was
used as the RNA probe for in situ hybridization, no labeled cells were seen
in normal or anemic livers. These results demonstrate that hepatocytes are
responsible for production of EPO in both transgenic and nontransgenic mice
and that a second cell type that is similar in morphology to EPO-producing
interstitial cells in the kidney also produces EPO in the livers of
nontransgenic mice.
Volume 77,
Issue 11,
pp. 2497-2503,
06/01/1991
Copyright © 1991 by The American Society of Hematology
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