THROMBOPOIETIN (TPO) mRNA EXPRESSION IN HUMAN FETAL AND NEONATAL ORGANS

Garle

Journal of Pharmaceutical and Biomedical Analysis

et al. 2013

The primary production site of erythropoietin (EPO) is shifted from the liver to the kidney shortly after birth. Under conditions of lost or reduced kidney production, it is valuable to measure the production capacity of the liver. However, there is a lack of urine or serum based methods that can distinguish endogenous EPO produced in different cell types. Here is presented a method based on chromatographic interaction with the lectin wheat germ agglutinin (WGA) that can distinguish presumably liver-produced EPO, found in anaemic patients receiving epoetin and darbepoetin, from kidney-produced EPO found in healthy individuals.All the tested samples from haemodialysis patients with end-stage renal disease showed a presence of liver EPO. In some samples, the liver-produced EPO made up 90-100% of total EPO at a concentration of 8-10 ng/L in urine, which indicates that the liver has a quite high production capacity, although not adequate for the degree of anaemia.This glycoform analysis has made it possible to affirm that some anaemic patients can increase their liver-production of EPO. The use of such a method can give better insight into the regulation of non-renal endogenous EPO production, a potential source of EPO intended to replace administration of exogenous EPO.

Section: Introductionmentioning

confidence: 99%

Patients with anaemia can shift from kidney to liver production of erythropoietin as shown by glycoform analysis

Garle

Journal of Pharmaceutical and Biomedical Analysis

et al. 2013

Journal of Biological Chemistry

“…The body weight ranged from 118 to 5627 g (median 656 g) and the crown-rump length from 18.1 to 64.5 cm (median 32.0 cm); these data were not evaluated in subjects with an age below 16 weeks pc. Technical procedures to collect the tissue biopsy specimens from liver (both right and left lobe) were performed as previously described (4). In addition to the patients' samples, we obtained RNA (liver, kidney, spinal cord, and CNS) from a commercially available panel, which included a liver sample from a 27-year-old Asian male (Clontech Laboratories Inc., Palo Alto, CA).…”

Section: Methodsmentioning

confidence: 99%

“…Fetal livers were homogenized in Isogen-TRIzol buffer (Nippongene, Inc.). The RNA was extracted, quality was assessed, and first-strand cDNA synthesis was performed as previously described (4). Semiquantitative RT-PCR was carried out with 1 l of cDNA (equivalent to 200 ng of total RNA), 21 l of PCR Platinum Supermix (Invitrogen), 5 Ci of [␣-…”

Section: Analysis Of Epo Gene Expression In Mice Bearing a Targetedmentioning

confidence: 99%

Hepatic Erythropoietin Gene Regulation by GATA-4

Dame

Sola

Lim

et al. 2004

Erythropoietin production switches from fetal liver to adult kidney during development. GATA transcription factors 2 and 3 could be involved in modulating this switch, because they were shown to negatively regulate erythropoietin gene transcription through a promoter proximal GATA site. Herein, we analyzed the role of several GATA factors in the regulation of the erythropoietin gene in human liver and in hepatoma cells. Although GATA-3 expression in hepatocytes increases during human development, erythropoietin mRNA accumulation is unaltered in mutant mice lacking GATA-3. We found that GATA-2, -3, -4, and -6 are all expressed in human hepatocytes and that GATA-4 exhibits the most prominent Epo promoter binding activity in vitro and in vivo. Inhibition of GATA-4 expression by RNA interference leads to a dramatic reduction in Epo gene transcription in Hep3B cells. Moreover, GATA-4 expression is high and limited to hepatocytes in the fetal liver, whereas GATA-4 expression in the adult liver is low and restricted to epithelial cells surrounding the biliary ducts. Thus, GATA-4 is critical for transcription of the Epo gene in hepatocytes and may contribute to the switch in the site of Epo gene expression from the fetal liver to the adult kidney.

Cancer Epidemiology, Biomarkers &Amp; Prevention

“…14). Indeed, in female reproductive organs, EPO/EPOR expression is regulated by estrogen and/or progesterone (15)(16)(17)(18)(19)(20). Nevertheless, no conclusive data exist on the correlation of EPO/EPOR with steroid receptors in normal mammary gland and breast carcinoma.…”

Section: Introductionmentioning

confidence: 99%

Erythropoietin and Its Receptor in Breast Cancer: Correlation with Steroid Receptors and Outcome

Pelekanou

Kampa

Kafousi³

et al. 2007

Autocrine/paracrine erythropoietin (EPO) action, promoting cell survival and mediated by its receptor (EPOR) in various solid tumors, including breast carcinoma, questions about the prognostic and therapeutic interest of this system. The expression of EPO/EPOR is steroid dependent in some tissues; however, a clear relationship of EPO/EPOR and steroid receptors in breast cancer has not been established thus far. Recently, the field of steroid receptors has expanded, including rapid effects mediated by membrane-associated receptors, regulating cell survival or apoptosis. The aim of this study was to evaluate EPO/EPOR and membrane-associated steroid receptor expression in breast carcinoma, in view of their prognostic significance, compared with other established markers [estrogen receptor (ER)-progesterone receptor (PR) status and Her2 expression] and hypoxia-induced factor 1 nuclear localization in 61 breast cancer specimens followed for V90 months. We report that EPO-EPOR were expressed in 80% and 84% of samples, although 8% and 2% of nontumoral fields expressed EPO/EPOR too. Membrane-associated receptors for estrogen (mER), progesterone (mPR), and androgen (mAR) were expressed in 96%, 94%, and 93% of cases. Significant correlations between EPO-hypoxiainduced factor 1A, mER-ER, mER-EPO, mAR-EPOR, and mER-mPR-Her2 were found. Finally, EPO, EPOR, and mAR are inversely related to disease-free and overall survival. However, in view of the above correlations, we conclude that EPO/EPOR and membrane steroid receptors are not independent prognostic markers as they are closely related to other established markers. In contrast, they may represent possible new therapeutic targets. (Cancer Epidemiol Biomarkers Prev 2007; 16(10):2016-23)