C/EBP-α, involvement of a novel transcription factor in leptin-induced VCAM-1 production in mouse chondrocytes

•Leptin induces C/EBP-α expression.•C/EBP-α regulates VCAM-1 expression by binding to a newly identified binding site in the VCAM-1 promoter region.•Leptin induces C/EBP-α-dependent VCAM-1 expression in chondrocytes. Leptin and vascular cell adhesion molecules-1 (VCAM-1) are two important mediators...

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Veröffentlicht in:FEBS letters 2014-04, Vol.588 (7), p.1122-1127
Hauptverfasser: Kang, Xia, Xie, Qing-Yun, Zhou, Jing-Song, Zhang, Bo, Liao, Dong-Fa, Wu, Hong-Hua, Zheng, Wei, Pan, Xian-Ming, Quan, Yi
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container_end_page 1127
container_issue 7
container_start_page 1122
container_title FEBS letters
container_volume 588
creator Kang, Xia
Xie, Qing-Yun
Zhou, Jing-Song
Zhang, Bo
Liao, Dong-Fa
Wu, Hong-Hua
Zheng, Wei
Pan, Xian-Ming
Quan, Yi
description •Leptin induces C/EBP-α expression.•C/EBP-α regulates VCAM-1 expression by binding to a newly identified binding site in the VCAM-1 promoter region.•Leptin induces C/EBP-α-dependent VCAM-1 expression in chondrocytes. Leptin and vascular cell adhesion molecules-1 (VCAM-1) are two important mediators in obesity-related osteoarthritis, while the molecular mechanism linking leptin to VCAM-1 production is still obscure. Here we show that leptin upregulates VCAM-1 mRNA and protein levels in a time- and dose-dependent manner. Mechanistically, leptin induces VCAM-1 promoter activity by increasing the expression of C/EBP-α and facilitating its binding to a newly identified element in the VCAM-1 gene. Gain or loss of function studies reveal a regulatory role of C/EBP-α on VCAM-1 expression. Finally, elevated plasma leptin level correlates to increased C/EBP-α and VCAM-1 production in chondrocytes from obese mice.
doi_str_mv 10.1016/j.febslet.2014.02.032
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Leptin and vascular cell adhesion molecules-1 (VCAM-1) are two important mediators in obesity-related osteoarthritis, while the molecular mechanism linking leptin to VCAM-1 production is still obscure. Here we show that leptin upregulates VCAM-1 mRNA and protein levels in a time- and dose-dependent manner. Mechanistically, leptin induces VCAM-1 promoter activity by increasing the expression of C/EBP-α and facilitating its binding to a newly identified element in the VCAM-1 gene. Gain or loss of function studies reveal a regulatory role of C/EBP-α on VCAM-1 expression. 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Leptin and vascular cell adhesion molecules-1 (VCAM-1) are two important mediators in obesity-related osteoarthritis, while the molecular mechanism linking leptin to VCAM-1 production is still obscure. Here we show that leptin upregulates VCAM-1 mRNA and protein levels in a time- and dose-dependent manner. Mechanistically, leptin induces VCAM-1 promoter activity by increasing the expression of C/EBP-α and facilitating its binding to a newly identified element in the VCAM-1 gene. Gain or loss of function studies reveal a regulatory role of C/EBP-α on VCAM-1 expression. Finally, elevated plasma leptin level correlates to increased C/EBP-α and VCAM-1 production in chondrocytes from obese mice.</description><subject>Animals</subject><subject>Binding Sites</subject><subject>C/EBP-α</subject><subject>CCAAT-enhancer-binding protein-α</subject><subject>CCAAT-Enhancer-Binding Proteins - physiology</subject><subject>Cells, Cultured</subject><subject>Chondrocytes - metabolism</subject><subject>Humans</subject><subject>Leptin</subject><subject>Leptin - physiology</subject><subject>Male</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Obesity - blood</subject><subject>Osteoarthritis</subject><subject>Primary Cell Culture</subject><subject>Promoter Regions, Genetic</subject><subject>RNA, Messenger - genetics</subject><subject>RNA, Messenger - metabolism</subject><subject>Vascular Cell Adhesion Molecule-1 - genetics</subject><subject>Vascular Cell Adhesion Molecule-1 - metabolism</subject><subject>vascular cell adhesion molecules-1</subject><subject>VCAM-1</subject><issn>0014-5793</issn><issn>1873-3468</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNkd1u1DAQhS0EotvCI4B8yUWT2k6cnyvUrrYUqVUr8XNrOfZEeJXYi51dtI_Fi_SZOmEXbsvVeOwzx6PzEfKOs5wzXl2s8x66NMCUC8bLnImcFeIFWfCmLrKirJqXZMHwJZN1W5yQ05TWDPuGt6_JiShlI-pWLkhYXqyuHrLH3-fU-V0YdjCCn2joqaY-7GCgU9Q-meg2kwue9tpMIaKWDoA3PnPebg1Y-n15eZdxuokB-z9S1Ixhm4CaH8HbGMx-gvSGvOr1kODtsZ6Rb9err8ub7Pb-0-fl5W1myqqQGa5nay7bTnaFNYa1nWAamlpWleGmZEZbIwTvddlwMLaBVraSl7o3PZZaFGfkw8EXF_q5hTSp0SUDw6A94FIKYxKYBZf181KJgbOilLOrPEhNDClF6NUmulHHveJMzVjUWh2xqBmLYkIhFpx7f_xi241g_0395YCCm4Pglxtg_3-u6np1Jb7MjGfEvMSTFLPVx4MVYLw7B1El48AjIxfBTMoG98y2T3iutrM</recordid><startdate>20140402</startdate><enddate>20140402</enddate><creator>Kang, Xia</creator><creator>Xie, Qing-Yun</creator><creator>Zhou, Jing-Song</creator><creator>Zhang, Bo</creator><creator>Liao, Dong-Fa</creator><creator>Wu, Hong-Hua</creator><creator>Zheng, Wei</creator><creator>Pan, Xian-Ming</creator><creator>Quan, Yi</creator><general>Elsevier B.V</general><scope>6I.</scope><scope>AAFTH</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>7QP</scope><scope>7TM</scope></search><sort><creationdate>20140402</creationdate><title>C/EBP-α, involvement of a novel transcription factor in leptin-induced VCAM-1 production in mouse chondrocytes</title><author>Kang, Xia ; 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subjects Animals
Binding Sites
C/EBP-α
CCAAT-enhancer-binding protein-α
CCAAT-Enhancer-Binding Proteins - physiology
Cells, Cultured
Chondrocytes - metabolism
Humans
Leptin
Leptin - physiology
Male
Mice
Mice, Inbred C57BL
Obesity - blood
Osteoarthritis
Primary Cell Culture
Promoter Regions, Genetic
RNA, Messenger - genetics
RNA, Messenger - metabolism
Vascular Cell Adhesion Molecule-1 - genetics
Vascular Cell Adhesion Molecule-1 - metabolism
vascular cell adhesion molecules-1
VCAM-1
title C/EBP-α, involvement of a novel transcription factor in leptin-induced VCAM-1 production in mouse chondrocytes
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