C Qiu1, X Liu, J Wang, Y Zhao, Q Fu. 1. Department of Orthopaedics, Shengjing Hospital of China Medical University, No. 36 San Hao Street, Shenyang, 110004, China.
Abstract
UNLABELLED: The expression of α2-Heremans-Schmid-glycoprotein (AHSG) was estrogen responsive in oophorectomized (OVX) osteopenic rats and HepG2 cells. Estrogen receptor α (ERα) interacted with the c-Jun/c-Fos heterodimer and indirectly associated with the -1488/-1482 activator protein-1 (AP-1) motif of the AHSG promoter. Estrogen increased c-Jun/c-Fos expression via the mitogen-activated protein kinase (MAPK) pathway. INTRODUCTION: AHSG is a hepatic secretory protein implicated in the regulation of bone homeostasis. Serum AHSG in women has been reported to decrease after menopause and increase with estrogen therapy. The detailed regulatory mechanism of estrogen on AHSG is unclear. METHODS: A postmenopausal osteoporosis model was generated in OVX rats. Skeletal parameters were determined by automatic biochemical analysis and dual X-ray absorptiometry. The expression of AHSG was evaluated by ELISA, real-time PCR, and Western blot. The 1.5-kb 5'-promoter region of AHSG was analyzed by serial truncation and luciferase assays. The putative -1488/-1482 AP-1 responsive element was identified by electrophoresis mobility shift assay (EMSA). Chromatin immunoprecipitation (ChIP), re-ChIP, and co-immunoprecipitation (Co-IP) were used to characterize the interaction of ERα and AP-1 at the -1488/-1482 AP-1 binding site. The MAPK pathway was evaluated using a specific inhibitor and active transfection. RESULTS: The expression of AHSG was estrogen responsive in both OVX rats and estradiol (E2)/ERα-treated HepG2 cells. E2/ERα most prominently increased luciferase activity of a construct with a putative -1488/-1482 AP-1 binding element. ERα interacted with the c-Jun/c-Fos heterodimer and indirectly associated with the -1488/-1482 AP-1 motif of the AHSG promoter. c-Jun/c-Fos expression was increased via the MAPK pathway by E2/ERα. CONCLUSION: Estrogen activated the transcription of AHSG through an indirect binding of ERα to the -1488/-1482 AP-1 binding element, with the c-Jun/c-Fos heterodimers.
UNLABELLED: The expression of α2-Heremans-Schmid-glycoprotein (AHSG) was estrogen responsive in oophorectomized (OVX) osteopenicrats and HepG2 cells. Estrogen receptor α (ERα) interacted with the c-Jun/c-Fos heterodimer and indirectly associated with the -1488/-1482 activator protein-1 (AP-1) motif of the AHSG promoter. Estrogen increased c-Jun/c-Fos expression via the mitogen-activated protein kinase (MAPK) pathway. INTRODUCTION:AHSG is a hepatic secretory protein implicated in the regulation of bone homeostasis. Serum AHSG in women has been reported to decrease after menopause and increase with estrogen therapy. The detailed regulatory mechanism of estrogen on AHSG is unclear. METHODS: A postmenopausal osteoporosis model was generated in OVX rats. Skeletal parameters were determined by automatic biochemical analysis and dual X-ray absorptiometry. The expression of AHSG was evaluated by ELISA, real-time PCR, and Western blot. The 1.5-kb 5'-promoter region of AHSG was analyzed by serial truncation and luciferase assays. The putative -1488/-1482 AP-1 responsive element was identified by electrophoresis mobility shift assay (EMSA). Chromatin immunoprecipitation (ChIP), re-ChIP, and co-immunoprecipitation (Co-IP) were used to characterize the interaction of ERα and AP-1 at the -1488/-1482 AP-1 binding site. The MAPK pathway was evaluated using a specific inhibitor and active transfection. RESULTS: The expression of AHSG was estrogen responsive in both OVX rats and estradiol (E2)/ERα-treated HepG2 cells. E2/ERα most prominently increased luciferase activity of a construct with a putative -1488/-1482 AP-1 binding element. ERα interacted with the c-Jun/c-Fos heterodimer and indirectly associated with the -1488/-1482 AP-1 motif of the AHSG promoter. c-Jun/c-Fos expression was increased via the MAPK pathway by E2/ERα. CONCLUSION: Estrogen activated the transcription of AHSG through an indirect binding of ERα to the -1488/-1482 AP-1 binding element, with the c-Jun/c-Fos heterodimers.
Authors: Majken K Jensen; Richard A Jensen; Kenneth J Mukamal; Xiuqing Guo; Jie Yao; Qi Sun; Marilyn Cornelis; Yongmei Liu; Ming-Huei Chen; Jorge R Kizer; Luc Djoussé; David S Siscovick; Bruce M Psaty; Joseph M Zmuda; Jerome I Rotter; Melissa Garcia; Tamara Harris; Ida Chen; Mark O Goodarzi; Michael A Nalls; Margaux Keller; Alice M Arnold; Anne B Newman; Ron C Hoogeveen; Kathryn M Rexrode; Eric B Rimm; Frank B Hu; Vasan S Ramachandran; Ronit Katz; James S Pankow; Joachim H Ix Journal: Hum Mol Genet Date: 2017-06-01 Impact factor: 5.121