|Platelet-derived growth factor signaling through ephrin-b2 regulates hepatic vascular structure and function.|
|PMID: 18570897 Owner: NLM Status: MEDLINE|
|BACKGROUND & AIMS: Cirrhosis is associated with prominent changes in sinusoidal structure and function. Although the resident pericyte in liver, the hepatic stellate cell (HSC), is well characterized in the process of fibrogenesis, signaling pathways that regulate HSC vascular function are less developed. Because pericyte populations outside the liver are increasingly being recognized as a key cell type for angiogenesis and changes in vascular structure, in this study, we explore new HSC-signaling pathways that regulate sinusoidal structure and function.
METHODS: Real-time video microscopy and quantitative software analysis of vascular tube formation were used to measure HSC angiogenesis in vitro. Platelet-derived growth factor (PDGF) and ephrin-signaling pathways were modulated using molecular and pharmacologic techniques. Complementary whole animal studies were performed to correlate in vitro findings with pericyte functions in vivo.
RESULTS: We show that PDGF promotes a phenotype of HSC evidenced by enhanced HSC-driven vascular tube formation in vitro and enhanced HSC coverage of sinusoids in vivo. This angiogenic phenotype modulates specific pericyte vascular functions including permeability and pressure regulation. Furthermore, we identify a key role for ephrin-B2 as a downstream effector of PDGF signaling.
CONCLUSIONS: These studies elucidate novel HSC-signaling pathways that regulate microvascular structure and function in liver.
|David Semela; Amitava Das; Daniel Langer; Ningling Kang; Edward Leof; Vijay Shah|
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|Type: Journal Article Date: 2008-04-16|
|Title: Gastroenterology Volume: 135 ISSN: 1528-0012 ISO Abbreviation: Gastroenterology Publication Date: 2008 Aug|
|Created Date: 2008-08-11 Completed Date: 2008-09-02 Revised Date: 2012-05-17|
Medline Journal Info:
|Nlm Unique ID: 0374630 Medline TA: Gastroenterology Country: United States|
|Languages: eng Pagination: 671-9 Citation Subset: AIM; IM|
|GI Research Unit/Fitterman Center for Digestive Disease, Mayo Clinic, Rochester, Minnesota, USA.|
|APA/MLA Format Download EndNote Download BibTex|
Disease Models, Animal
Dose-Response Relationship, Drug
Endothelial Cells / drug effects, metabolism*
Ephrin-B2 / genetics, metabolism*
Hypertension, Portal / metabolism, physiopathology
Image Processing, Computer-Assisted
Liver / blood supply*
NIH 3T3 Cells
Neovascularization, Physiologic* / drug effects
Pericytes / drug effects, metabolism*
Piperazines / pharmacology
Platelet-Derived Growth Factor / metabolism*
Protein Kinase Inhibitors / pharmacology
Pyrimidines / pharmacology
Receptors, Platelet-Derived Growth Factor / antagonists & inhibitors, metabolism
Signal Transduction* / drug effects
|R01 DK059388-05/DK/NIDDK NIH HHS; R01 DK059615/DK/NIDDK NIH HHS; R01 DK059615-06A1/DK/NIDDK NIH HHS; R01 DK059615-09/DK/NIDDK NIH HHS|
|0/Ephrin-B2; 0/Piperazines; 0/Platelet-Derived Growth Factor; 0/Protein Kinase Inhibitors; 0/Pyrimidines; 0/platelet-derived growth factor BB; 152459-95-5/imatinib; EC 18.104.22.168/Receptors, Platelet-Derived Growth Factor|
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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