Differential gene expression of MMP-1, TIMP-1 and HGF in clinically involved and uninvolved skin in South Africans with SSc

被引:30
作者
Frost, Jacqueline [1 ,2 ,3 ]
Ramsay, Michele [2 ,3 ]
Mia, Ridwan [4 ]
Moosa, Laeeka [5 ]
Musenge, Eustasius [6 ]
Tikly, Mohammed [1 ]
机构
[1] Chris Hani Baragwanath Acad Hosp, Fac Hlth Sci, Div Rheumatol, Dept Med, Johannesburg, South Africa
[2] Univ Witwatersrand, Fac Hlth Sci, Natl Hlth Lab Serv, Div Human Genet, Johannesburg, South Africa
[3] Univ Witwatersrand, Fac Hlth Sci, Sch Pathol, Johannesburg, South Africa
[4] Univ Witwatersrand, Fac Hlth Sci, Div Plast & Reconstruct Surg, Johannesburg, South Africa
[5] Univ Witwatersrand, Dept Med, Fac Hlth Sci, Div Dermatol, ZA-2001 Johannesburg, South Africa
[6] Univ Witwatersrand, Fac Hlth Sci, Sch Publ Hlth, Johannesburg, South Africa
关键词
scleroderma; fibrosis; tissue inhibitor of metalloproteinase-1; matrix metalloproteinase-1; hepatocyte growth factor; African; HEPATOCYTE GROWTH-FACTOR; SYSTEMIC-SCLEROSIS; SCLERODERMA SKIN; C-MET; FIBROBLASTS; COLLAGEN; IDENTIFICATION; ASSOCIATION; INHIBITOR; DISEASE;
D O I
10.1093/rheumatology/ker367
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Objective. To investigate the differential expression of MMP-1, tissue inhibitor of metalloproteinase-1 (TIMP-1) and hepatocyte growth factor (HGF) in clinically involved (affected) and uninvolved (unaffected) skin in patients with SSc. Methods. Punch biopsies from affected forearm and unaffected upper back skin of 16 black South Africans with dcSSc and skin samples of 15 ethnically matched healthy controls were studied. Quantitative mRNA expression of MMP-1, TIMP-1 and HGF was performed by relative reverse transcription quantitative PCR. Results. Compared with controls, TIMP-1 expression was significantly upregulated in patients, a 796- and 397-fold difference for affected and unaffected skin (P < 0.00001 for both), respectively. Conversely, MMP-1 expression was significantly decreased in patients, a 10- and 12.5-fold difference for affected and unaffected skin (P = 0.0004 for both), respectively. HGF expression was up-regulated in both affected and unaffected skin, a 14- and 18-fold difference (P = 0.004 and P = 0.002), respectively. Within the patient group, HGF expression in affected skin of patients correlated significantly with the European scleroderma disease activity score (r = 0.60, P = 0.013). Conclusion. Perturbations in gene expression of TIMP-1, MMP-1 and HGF were evident in both affected and unaffected skin of the dcSSc patients. Targeting TIMP-1, which showed the greatest dysregulation, needs to be explored as a way of reducing collagen deposition and fibrosis in dcSSc.
引用
收藏
页码:1049 / 1052
页数:4
相关论文
共 29 条
[11]  
Kawaguchi Y, 1999, J RHEUMATOL, V26, P1012
[12]  
Kawaguchi Y, 2002, J RHEUMATOL, V29, P1877
[13]   MYOFIBROBLASTS FROM SCLERODERMA SKIN SYNTHESIZE ELEVATED LEVELS OF COLLAGEN AND TISSUE INHIBITOR OF METALLOPROTEINASE (TIMP-1) WITH 2 FORMS OF TIMP-1 [J].
KIRK, TZ ;
MARK, ME ;
CHUA, CC ;
CHUA, BH ;
MAYES, MD .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1995, 270 (07) :3423-3428
[14]   Persistent down-regulation of Fli1, a suppressor of collagen transcription, in fibrotic scleroderma skin [J].
Kubo, M ;
Czuwara-Ladykowska, J ;
Moussa, O ;
Markiewicz, M ;
Smith, E ;
Silver, RM ;
Jablonska, S ;
Blaszczyk, M ;
Watson, DK ;
Trojanowska, M .
AMERICAN JOURNAL OF PATHOLOGY, 2003, 163 (02) :571-581
[15]   Racial differences in scleroderma among women in Michigan [J].
Laing, TJ ;
Gillespie, BW ;
Toth, MB ;
Mayes, MD ;
Gallavan, RH ;
Burns, CJ ;
Johanns, JR ;
Cooper, BC ;
Keroack, BJ ;
Wasko, MCM ;
Lacey, JV ;
Schottenfeld, D .
ARTHRITIS AND RHEUMATISM, 1997, 40 (04) :734-742
[16]  
LEROY EC, 1988, J RHEUMATOL, V15, P202
[17]   Analysis of relative gene expression data using real-time quantitative PCR and the 2-ΔΔCT method [J].
Livak, KJ ;
Schmittgen, TD .
METHODS, 2001, 25 (04) :402-408
[18]  
Sherriff-Tadano Ryoko, 2006, Mod Rheumatol, V16, P364, DOI 10.1007/s10165-006-0525-z
[19]   Hepatocyte Growth Factor Inhibits Epithelial to Myofibroblast Transition in Lung Cells via Smad7 [J].
Shukla, Manasi N. ;
Rose, Jane L. ;
Ray, Rabindranath ;
Lathrop, Kira L. ;
Ray, Anuradha ;
Ray, Prabir .
AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY, 2009, 40 (06) :643-653
[20]   Clinical and laboratory manifestations of systemic sclerosis (scleroderma) in Black South Africans [J].
Tager, RE ;
Tikly, M .
RHEUMATOLOGY, 1999, 38 (05) :397-400