Document Detail


Venous ulcer fibroblasts respond to basic fibroblast growth factor at the cell cycle protein level.
MedLine Citation:
PMID:  16609829     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Fibroblasts cultured from venous ulcers demonstrate phenotypic characteristics of cellular senescence including slow growth, altered morphology, upregulation of fibronectin, and increased senescence-associated beta-galactosidase activity. In senescent cells, arrest of cell replication is related to overexpression of p21 and underexpression of phosphorylated tumor-suppressor protein retinoblastoma (ppRb). The regulatory mechanisms for cell proliferation in venous ulcer fibroblasts are unknown. In this study, venous ulcer fibroblasts are examined for cell cycle protein expression and modulation by basic fibroblast growth factor (bFGF). Fibroblasts were isolated from the venous ulcer of the distal lower extremity (fb-D) of patients with chronic venous insufficiency. A control biopsy was obtained from the proximal ipsilateral thigh (fb-P). Paired cultures were plated at 100,000 cells/plate and the cells synchronized. After 24 hr, one culture set was treated with bFGF (20 ng/mL) and the other was kept in culture medium only (untreated). All cultures, treated and untreated, were lysed following 24 hr of incubation, and the lysate was used to perform immunoblot analysis for p21, ppRb, and cyclin D1. Immunoblot samples were standardized to protein content. In all patients analyzed (n = 4), at basal levels (untreated) fb-D demonstrated significant overexpression of p21 versus fb-P (p = 0.016). Treatment with bFGF resulted in significant downregulation of p21 levels for fb-D (p = 0.008) and fb-P (p = 0.037) compared to untreated fibroblasts. ppRb was underexpressed in fb-D versus fb-P (p = 0.069). Treatment with bFGF increased ppRb significantly in fb-D (p = 0.030) and in fb-P (p = 0.027) compared to untreated fibroblasts. No differences were observed in cyclin D1 with respect to basal levels in fb-P versus fb-D or in treated versus untreated groups. Venous ulcer fibroblasts show phenotypic similarity to senescent cells, with overexpression of p21 as well as down regulation of phosphorylated pRb. The aberrations seen in the cell cycle proteins in fb-D are similar to those seen in senescent cells; however, bFGF can modulate important cell cycle regulatory proteins, promoting a proliferative environment in fb-D that is not possible in a senescent cell. The role of bFGF may be useful in the clinical treatment of venous ulcer pathology.
Authors:
Craig Seidman; Joseph D Raffetto; Kristen C Overman; James O Menzoian
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Publication Detail:
Type:  Comparative Study; Journal Article     Date:  2006-04-12
Journal Detail:
Title:  Annals of vascular surgery     Volume:  20     ISSN:  0890-5096     ISO Abbreviation:  Ann Vasc Surg     Publication Date:  2006 May 
Date Detail:
Created Date:  2006-06-16     Completed Date:  2006-11-09     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  8703941     Medline TA:  Ann Vasc Surg     Country:  United States    
Other Details:
Languages:  eng     Pagination:  376-80     Citation Subset:  IM    
Affiliation:
Eugene Surgical Associates Peacehealth, Eugene, OR, USA.
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MeSH Terms
Descriptor/Qualifier:
Adult
Cell Proliferation
Cells, Cultured
Cyclin D
Cyclin-Dependent Kinase Inhibitor p21 / metabolism*
Cyclins / metabolism
Female
Fibroblast Growth Factor 2 / pharmacology*
Fibroblasts / drug effects*,  metabolism,  pathology
Humans
Male
Middle Aged
Phosphorylation
Retinoblastoma Protein / metabolism*
Varicose Ulcer / pathology*
Venous Insufficiency / pathology*
Chemical
Reg. No./Substance:
0/CDKN1A protein, human; 0/Cyclin D; 0/Cyclin-Dependent Kinase Inhibitor p21; 0/Cyclins; 0/Retinoblastoma Protein; 103107-01-3/Fibroblast Growth Factor 2

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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