Cookies on this website

We use cookies to ensure that we give you the best experience on our website. If you click 'Accept all cookies' we'll assume that you are happy to receive all cookies and you won't see this message again. If you click 'Reject all non-essential cookies' only necessary cookies providing core functionality such as security, network management, and accessibility will be enabled. Click 'Find out more' for information on how to change your cookie settings.

We have used in situ hybridization to determine the localization and distribution of cells expressing the erythropoietin (EPO) gene in kidneys of rats exposed to reduced oxygen tensions to characterize the control of renal EPO formation during hypoxic hypoxia. Animals were subjected to severe hypoxia (7.5% O2) for 4, 8 and 32 hours to assess changes related to the duration of hypoxic exposure, and additionally to 9% and 11.5% O2 for eight hours to define changes related to the degree of hypoxia. The number of cells containing EPO mRNA were counted on tissue sections and compared to tissue concentrations of EPO mRNA and to the serum hormone concentrations. In situ hybridization revealed expression of the EPO gene exclusively in peritubular cells that were predominantly located in the cortical labyrinth under all conditions tested. After four hours of severe hypoxia (7.5% O2) approximately 170-fold more cells were found to contain EPO mRNA than under normoxic conditions. The number of EPO producing cells did not change significantly between four and eight hours exposure to 7.5% O2, but the amount of EPO mRNA per kidney increased approximately threefold. Further continuation of hypoxia resulted in down-regulation of renal EPO mRNA levels, which was mainly due to a reduction in the number of cells containing EPO mRNA. Comparison of graded degrees of hypoxia applied for eight hours showed an inverse exponential relationship between oxygen tension and the number of EPO producing cells. This recruitment of cells expressing the EPO gene occurred along a gradient extending from the corticomedullary border to the subcapsular tissue.(ABSTRACT TRUNCATED AT 250 WORDS)


Journal article


Kidney Int

Publication Date





815 - 823


Anemia, Animals, Erythropoietin, Gene Expression, Hypoxia, In Situ Hybridization, Kidney, Male, RNA, Messenger, Rats, Time Factors, Tissue Distribution