Fibroblasts cultured from venous ulcers display cellular characteristics of senescence

被引:148
作者
Mendez, MV
Stanley, A
Park, HY
Shon, K
Phillips, T
Menzoian, JO
机构
[1] Boston Univ, Med Ctr, Dept Surg, Vasc Surg Sect, Boston, MA 02118 USA
[2] Boston Univ, Med Ctr, Dept Dermatol, Boston, MA 02118 USA
关键词
D O I
10.1016/S0741-5214(98)70064-3
中图分类号
R61 [外科手术学];
学科分类号
摘要
Purpose: A well-recognized characteristic of venous ulcers is impaired healing. Fibroblasts cultured from venous ulcers (wound-fb) have been shown to have reduced growth rates and are larger than normal fibroblasts (normal-fb) from the ipsilateral Limb. Reduced growth capacity and morphologic changes are 2 well-known traits of cellular senescence. Other molecular changes are overexpression of matrix proteins, such as cellular fibronectin (cFN), and enhanced activity of P-galactosidase at pH of 6.0 (senescence associated beta-Gal, or SA-beta-Gal). Senescence, an irreversible arrest of cell proliferation with maintenance of metabolic functions, may represent in vivo aging and thus may be related to impaired healing. Methods: Cultured normal-fb and wound-fb from 7 venous ulcer patients (average age, 51 years) were obtained by taking punch biopsies of the perimeter of the ulcer and from the ipsilateral thigh of the same patient. Growth rates, SA-beta-Gal activity and level of cFN protein (immunoblot) and message (Northern blot) were measured. Results: In all patients, wound-fb growth rates were significantly lower than those of normal-fb (P = .006). A higher percentage of SA-beta-Gal positive cells were found in all wound-fb (average, 6.3% vs. 0.21%; P = .016). The level of cFN, was consistently higher in all wound-fb tested Also, in 4 patients, the level of cFN messenger. RNA (mRNA) was increased. Conclusion: Fibroblasts cultured from venous ulcers exhibited characteristics associated with senescent cells. Accumulation of senescent cell in ulcer environment may be associated with impaired healing.
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页码:876 / 883
页数:8
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共 34 条
[21]  
LABATROBERT J, 1991, CR SOC BIOL, V185, P121
[22]   Identification of gene sequences overexpressed in senescent and Werner syndrome human fibroblasts [J].
LeckaCzernik, B ;
Moerman, EJ ;
Jones, RA ;
Goldstein, S .
EXPERIMENTAL GERONTOLOGY, 1996, 31 (1-2) :159-174
[23]  
LOK C, 1991, J MAL VASCUL, V16, P381
[24]  
MARTIN GM, 1970, LAB INVEST, V23, P86
[25]  
PIERCE GF, 1995, ANNU REV MED, V46, P467
[26]  
Sarin Sanjeev, 1993, Journal of Vascular Surgery, V17, P444
[27]  
SCHNEIDER EL, 1972, P SOC EXP BIOL MED, V141, P1092
[28]   RELATIONSHIP BETWEEN INVITRO CELLULAR AGING AND INVIVO HUMAN AGE [J].
SCHNEIDER, EL ;
MITSUI, Y .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1976, 73 (10) :3584-3588
[29]   RISK-FACTORS FOR CHRONIC VENOUS INSUFFICIENCY - A DUAL CASE-CONTROL STUDY [J].
SCOTT, TE ;
LAMORTE, WW ;
GORIN, DR ;
MENZOIAN, JO .
JOURNAL OF VASCULAR SURGERY, 1995, 22 (05) :622-628
[30]   Reduced growth of dermal fibroblasts from chronic venous ulcers can be stimulated with growth factors [J].
Stanley, AC ;
Park, HY ;
Phillips, TJ ;
Russakovsky, V ;
Menzoian, JO .
JOURNAL OF VASCULAR SURGERY, 1997, 26 (06) :994-999