Localization of Erythropoietin in the Glomerulus of the Hypoxic Dog Kidney Using a Fluorescent Antibody Technique

Busuttil, Ronald W.; Roh, Byung L.; Fisher, James W.

doi:10.1159/000208530

Cited by 32 publications

(6 citation statements)

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“…Moreover, the localization of Epo production to the peritubular cells does not exclude a role for the other kidney cells in the storage of Epo. Indeed, previous data suggesting that glomerular cells produce Epo were mostly obtained using immunofluorescence techniques (3,4), which do not distinguish between production and storage of a protein.…”

Section: Resultsmentioning

confidence: 99%

“…However, the identity of the kidney cells that are responsible for Epo biosynthesis is still a matter ofcontroversy. A glomerular origin for renal Epo has been suggested based on immunohistochemical studies (3,4) and on studies about Epo production by in vitro cultured glomerular (5) and mesangial (6) cells. Proximal tubular cells have also been considered by others as primary candidates for Epo production (7).…”

Section: Introductionmentioning

confidence: 99%

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Peritubular cells are the site of erythropoietin synthesis in the murine hypoxic kidney.

Lacombe

Silva²,

Bruneval³

et al. 1988

J. Clin. Invest.

414

163

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Erythropoietin (Epo)-producing cells were identified in the murine hypoxic kidney by in situ hybridization. Profound anemia was induced in order to greatly increase Epo production. This resulted in high levels of Epo mRNA in the kidney. 35S-labeled DNA fragments of the murine Epo gene were used as probes for in situ hybridization. Control experiments conducted in parallel included kidneys of nonanemic mice, RNase-treated hypoxic kidney sections, and 35S-labeled nonEpo-related DNA. The Epo probe gave a specific hybridization signal in the hypoxic kidney in the cortex and to a lesser extent in the outer medulla. Glomerular and tubular cells were not labeled. All positive cells were identified as peritubular cells.Using immunofluorescence, we showed that cells with the same topography contained Factor VIII-related antigen. These data demonstrated that peritubular cells, most likely endothelial cells, constitute the major site of Epo production in the murine hypoxic kidney.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Peritubular cells are the site of erythropoietin synthesis in the murine hypoxic kidney.

Lacombe

Silva²,

Bruneval³

et al. 1988

J. Clin. Invest.

414

163

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“…Those studies localized EPO in the glomerular tuft of an anemic-sheep kidney (Fisher et al 1965 ;Frenkel et al 1968). Busuttil et al (1971Busuttil et al ( , 1972 reported, by the same method that the epithelial cell of the glomerular tuft in both the human and hypoxic dog kidney was the most likely source of EPO. The anti-EPO sera used by the latter researchers were anti-crude human EPO rabbit serum and those used by the former researchers were anti-partially purified sheep EPO rabbit serum.…”

Section: )mentioning

confidence: 96%

Localization of renal erythropoietin and the role of Ia antigen expression in hypoxic rat glomeruli.

Fukushima

Yanagisawa

Nakamoto

et al. 1990

Tohoku J. Exp. Med.

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Erythropoietin (EPO) producing cells were examined by the immunofluorescent antibody technique, and the alterations in the Ia antigen expression in glomeruli by hypoxic stimuli. Antisera were obtained from rabbits immunized with pure human EPO. Positive fluorescence was localized in glomerular mesangial regions of the hypoxic rat kidney. Although hypoxia showed neither increase in the number of glomerular cells nor hypertrophy of the mesangial matrix, it induced an increase of the Ia antigen expressions in glomeruli. The peak of the increase occurred 2 hr after hypoxia and then decreased until 24 hr later. The increase of Ia antigen after 2 hr of hypoxic stimuli was 176.5 + 7.0% of normal controls, and ranged from 151 to 209%. In conclusion, Ia positive cells in glomeruli may have some relationship to the stimulation of EPO production. erythropoietin (EPO) ; Ia antigen ; hypoxia Erythropoietin (EPO) is the glycoprotein hormone which is the primary factor regulating erythropoiesis, and is produced by the kidney. Although the molecular structure of EPO has been described earlier (Jacobs et al. 1985 ;Lin et al. 1985), the producing cells or sites have remained unclear. There are many reports about the localization of EPO production within the kidney. The cells responsible for EPO production are most probably localized in the kidney cortex. Significantly more EPO was extracted from the cortex than from the medulla.

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“…Several groups have used either immunofluorescence or immunocytochemistry to localize EPO-producing cells in the kidney and have obtained conflicting results. Glomerular (Busuttil et al, 1972;Fisher et al, 1965;Mori et al, 1985), tubular (Maxwell et al, 1990), and peritubular (Suzuki and Sasaki, 1990) cells have all been proposed to be the source of EPO using such methods. A problem with these immunological methods is that since EPO circulates in plasma and is excreted in urine, they could not distinguish between production, nonspecific adherence, were classified asbeing nonepithelial based on sinusoids.…”

Section: Introductionmentioning

confidence: 99%

The use of in situ hybridization to study erythropoietin gene expression in murine kidney and liver

Koury

Bondurant

Semenza

et al. 1993

Microscopy Res & Technique

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In situ hybridization has been used to localize erythropoietin (EPO)-producing cells in murine kidney and liver. Peritubular interstitial cells were the only cell type that produced EPO in the kidney. The EPO-producing cells were primarily concentrated in the inner cortex but were also seen in the outer medulla and outer cortex. EPO-producing cells represented less than 10% of the total interstitial cell population. The number of EPO-producing cells per square centimeter of cortex directly correlated with the amount of renal EPO mRNA and varied in an inverse exponential manner with hematocrit. These results suggest that EPO is expressed in an all-or-none fashion in peritubular interstitial cells and that the oxygen carrying capacity of blood is the major regulator of renal EPO production. Peritubular interstitial cells were also identified as the renal source of human EPO in transgenic mice that expressed human EPO mRNA is a regulated fashion in the kidney. Transgenic mice exhibiting inducible supranormal liver expression of human EPO were used to identify EPO-producing cells in the liver. Hepatocytes surrounding central veins produced human EPO in these mice. Individual hepatocytes were able to modulate their production of human EPO depending upon the severity of anemia to which they were subjected. Two types of widely scattered cells produced EPO in severely anemic nontransgenic mice. Eighty percent of EPO-producing cells were hepatocytes and 20% were classified as being nonepithelial based on their nuclear morphology and location in venous sinusoids.

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Localization of Erythropoietin in the Glomerulus of the Hypoxic Dog Kidney Using a Fluorescent Antibody Technique

Cited by 32 publications

References 5 publications

Peritubular cells are the site of erythropoietin synthesis in the murine hypoxic kidney.

Peritubular cells are the site of erythropoietin synthesis in the murine hypoxic kidney.

Localization of renal erythropoietin and the role of Ia antigen expression in hypoxic rat glomeruli.

The use of in situ hybridization to study erythropoietin gene expression in murine kidney and liver

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