Erythropoietin production in kidney tubular cells

Abstract

The erythropoietin gene has been cloned in three mammalian species including man and recombinant erythropoietin is now used to treat the anaemia of chronic renal failure. Despite the isolation of the gene the precise cellular location of erythropoietin synthesis remains controversial. We present studies which demonstrate erythropoietin production by kidney tubular cells. Erythropoietin gene expression (messenger RNA) was detected by in situ hybridization using an oligonucleotide gene probe and the translated protein product by immunohistochemistry employing antibodies raised to pure recombinant DNA derived erythropoietin.

Identification of Renox, an NAD(P)H oxidase in kidney

“…Although it is generally accepted that EPO is produced in the renal cortex, there are conflicting reports on the exact cellular source of the hormone. Several studies, including one that used a transgenic approach, indicated that EPO is produced by the proximal convoluted tubule cells (7,17), and others that used similar experimental techniques detected the EPO mRNA exclusively in the peritubular interstitial cells in the renal cortex (8,18). This disparity, however, is likely unimportant in terms of location of the oxygen sensor, because long-lived ROS such as hydrogen peroxide are membrane permeable and would readily diffuse into neighboring cells.…”

Acute Normobaric Hypoxia Stimulates Erythropoietin Release

“…It is clear from the data in the current study that EPO release is subject to a distinct difference in the level of response, with values ranging from Ϫ5.6% to 61.8% (mean, ⌬21%). The production of EPO is noticeably augmented by the depression of Ca O 2 , resulting from decreases in oxyhemoglobin saturation (Sp O 2 ), (Eckardt et al, 1993;Maxwell et al, 1990). Thus, a greater reduction in Sp O 2 com-MACKENZIE ET AL.…”

Physiology of the Renal Interstitium

“…However, Epo expression levels are low, and immunolabeling and in situ hybridization analyses proved to be unreliable; it took extensive studies using transgenic mice to finally, unequivocally identify renal interstitial fibroblasts as primary producers of Epo (16,(40)(41)(42). Furthermore, analysis of Epo expression in vivo is technically challenging because large regions of noncoding DNA flanking the Epo locus (which contains tissue-specific enhancers and repressors) must be included to adequately reflect endogenous Epo expression.…”