title: Decoupled syndecan 1 mRNA and protein expression is differentially regulated by angiotensin II in macrophages.
abstract: It has been established that syndecan-1 is an important modulator of events relevant to acute tissue repair and chronic injury responses. The current studies were designed to examine syndecan-1 expression during atherosclerotic lesion formation and whether angiotensin II influences syndecan-1 expression in macrophages. ApoE knockout mice maintained on an atherogenic diet were treated for 8 weeks with an infusion of angiotensin II to induce atherosclerosis. Immunohistochemistry was employed to characterize the expression of syndecan-1 in atherosclerotic lesions. Quantitative real-time PCR (QRTPCR) was used to define the role of angiotensin II and responsible signaling pathways involved syndecan-1 expression in RAW264.7 murine macrophages. Protein expression and shedding were characterized by fluorescence activated cell sorting (FACS) and slot blot analysis. Syndecan-1 was abundantly expressed in macrophages located within early atherosclerotic lesions. Accordingly, we hypothesized that angiotensin II regulates syndecan-1 expression in macrophages. A time- and dose-dependent study was performed in RAW264.7 macrophages. QRTPCR demonstrated maximum syndecan-1 mRNA up-regulation at 6 h after 500 nM AgII stimulation (threefold; P < 0.05). Through administration of specific inhibitors, we established that ERK/MAPK, PI3K and JNK signaling pathways mediated this effect. FACS and slot blot analyses demonstrated that cAMP induced posttranscriptional syndecan-1 protein expression in a dose-dependent manner with or without initial angiotensin II stimulation. In particular, angiotensin II induced an increase in cell surface syndecan-1 (mean fluorescence intensity: 147 +/- 5.7 vs. 176 +/- 4.8; P < 0.05; n = 3) and accelerated syndecan-1 shedding. Angiotensin II is a potent regulator of syndecan-1 expression in atherosclerotic lesions via a specific effect on macrophages that is mediated by ERK/MAPK, PI3K, and JNK signaling pathways.
authors: Departments of Surgery and Biomedical Engineering, Emory University, Atlanta, Georgia, USA.
authors: Wenli
authors: W
authors: Wang
authors: Carolyn A
authors: CA
authors: Haller
authors: Jing
authors: J
authors: Wen
authors: Peiyi
authors: P
authors: Wang
authors: Elliot L
authors: EL
authors: Chaikof
mesh_terms: D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000473:pathology; D050197:Atherosclerosis / Q000378:metabolism; D003994:Bucladesine / Q000494:pharmacology; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D005786:Gene Expression Regulation / Q000187:drug effects*; D008264:Macrophages / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D053668:Syndecan-1 / Q000235:genetics* / Q000378:metabolism*; D013997:Time Factors; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D012333:RNA, Messenger; D053668:Syndecan-1; D000804:Angiotensin II; D003994:Bucladesine