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Renal LRP2 expression in man and chicken is estrogen-responsive.

ABSTRACT: In mammals, low-density lipoprotein receptor-related protein-2 (LRP2) is an endocytic receptor that binds multiple ligands and is essential for a wide range of physiological processes. To gain new insights into the biology of this complex protein, we have initiated the molecular characterization of the LRP2 homolog from an oviparous species, the chicken (Gallus gallus). The galline LRP2 cDNA encodes a membrane protein of 4658 residues. Overall, the galline and human proteins are 73% identical, indicating that the avian gene has been well conserved over 300 million years. Unexpectedly, LRP2 transcript and protein levels in the kidney of females and estrogen-treated roosters were significantly higher than those in untreated males. The estrogen-responsiveness of avian LRP2 may be related to the dramatic differences in lipoprotein metabolism between mature roosters and laying hens. Newly identified potential estrogen-responsive elements (ERE) in the human and galline LRP2 gene, and additional Sp1 sites present in the promoter of the chicken gene, are compatible with both direct estrogen induction via the classical ligand-induced ERE pathway and the indirect transcription factor crosstalk pathway engaging the Sp1 sites. In agreement with this assumption, estrogen induction of LRP2 was observed not only in primary cultured chicken kidney cells, but also human kidney cell lines. These findings point to novel regulatory features of the LRP2 gene resulting in sex-specific receptor expression.

SUBMITTER: Plieschnig JA

PROVIDER: S-EPMC3443750 | biostudies-literature | 2012 Oct

REPOSITORIES: biostudies-literature

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Renal LRP2 expression in man and chicken is estrogen-responsive.

Plieschnig Julia A JA Gensberger Eva T ET Bajari Tarek M TM Schneider Wolfgang J WJ Hermann Marcela M

Gene 20120731 1

In mammals, low-density lipoprotein receptor-related protein-2 (LRP2) is an endocytic receptor that binds multiple ligands and is essential for a wide range of physiological processes. To gain new insights into the biology of this complex protein, we have initiated the molecular characterization of the LRP2 homolog from an oviparous species, the chicken (Gallus gallus). The galline LRP2 cDNA encodes a membrane protein of 4658 residues. Overall, the galline and human proteins are 73% identical, i ...[more]

PMID: 22868208

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Project description:In women, the flow of psoriasis is influenced by each phase of a woman's life cycle. According to previous findings, significant changes in the levels of sex hormones affect the severity of the disease. Aim: The aim of this study was to identify the estrogen-responsive genes that could be responsible for the exacerbation of psoriasis in menopausal women. Methods: Skin samples of lesional skin donated by psoriasis patients (n = 5) were compared with skin samples of healthy volunteers (n = 5) using liquid chromatography-tandem mass spectrometry (LC-MS/MS). The set of differentially expressed proteins was subjected to protein ontology analysis to identify differentially expressed estrogen-responsive proteins. The expression of discovered proteins was validated by qPCR and ELISA on four groups of female participants. The first group included ten psoriasis patients without menopause; the second included eleven postmenopausal patients; the third included five healthy volunteers without menopause; and the fourth included six postmenopausal volunteers. Moreover, the participants' blood samples were used to assess the levels of estradiol, progesterone, and testosterone. Results: We found that the levels of estradiol and progesterone were significantly lower and the levels of testosterone were significantly higher in the blood of patients compared to the control. The protein ontology analysis of LC-MS/MS data identified six proteins, namely HMOX1, KRT19, LDHA, HSPD1, MAPK1, and CA2, differentially expressed in the lesional skin of female patients compared to male patients. ELISA and qPCR experiments confirmed differential expression of the named proteins and their mRNA. The genes encoding the named proteins were differentially expressed in patients compared to volunteers. However, KRT19 and LDHA were not differentially expressed when we compared patients with and without menopause. All genes, except MAPK1, were differentially expressed in patients with menopause compared to the volunteers with menopause. HMOX1, KRT19, HSPD1, and LDHA were differentially expressed in patients without menopause compared to the volunteers without menopause. However, no significant changes were found when we compared healthy volunteers with and without menopause. Conclusion: Our experiments discovered a differential expression of six estrogen-controlled genes in the skin of female patients. Identification of these genes and assessment of the changes in their expression provide insight into the biological effects of estrogen in lesional skin. The results of proteomic analysis are available via ProteomeXchange with identifier PXD021673.

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Dataset Information

Renal LRP2 expression in man and chicken is estrogen-responsive.

Publications

Renal LRP2 expression in man and chicken is estrogen-responsive.

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