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result sql = SIRT1 modulates expression of matrix metalloproteinases in human dermal fibroblasts.
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result sql = BACKGROUND : SIRT1, an NAD(+) -dependent histone/protein deacetylase, controls a broad range of cellular functions.
OBJECTIVES : We examined if SIRT1 is involved in the regulation of matrix metalloproteinase (MMP) expression in human dermal fibroblasts.
METHODS : We studied the effect of inhibition of SIRT1 by specific inhibitor and small interfering RNA (siRNA) on MMP-1 and MMP-3 expression in human dermal fibroblasts.
RESULTS : Treatment with a potent and selective inhibitor of SIRT1, EX-527, increased the basal expression levels of MMP-1 and MMP-3 proteins. Knockdown of endogenous SIRT1 by siRNA led to increased expression of MMP-1 and MMP-3 at both mRNA and protein levels. SIRT1 knockdown also upregulated MMP protein induction caused by an inflammatory cytokine, interleukin (IL)-1β. Moreover, treatment with a SIRT1 activator, resveratrol, significantly suppressed IL-1β-mediated induction of MMP-1, which was attenuated by pretreatment with EX-527. Finally, MMP-1 promoter activity was increased by EX-527 in cells treated with or without IL-1β.
CONCLUSIONS : Our findings suggest that SIRT1 exerts a negative regulatory role in the production of MMP-1 and MMP-3 in human dermal fibroblasts.
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result sql = SIRT1 modulates expression of matrix metalloproteinases in human dermal fibroblasts.
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char = ;code = 32
char = b;code = 98
char = y;code = 121
char = ;code = 32
char = s;code = 115
char = p;code = 112
char = e;code = 101
char = c;code = 99
char = i;code = 105
char = f;code = 102
char = i;code = 105
char = c;code = 99
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = h;code = 104
char = i;code = 105
char = b;code = 98
char = i;code = 105
char = t;code = 116
char = o;code = 111
char = r;code = 114
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = s;code = 115
char = m;code = 109
char = a;code = 97
char = l;code = 108
char = l;code = 108
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = t;code = 116
char = e;code = 101
char = r;code = 114
char = f;code = 102
char = e;code = 101
char = r;code = 114
char = i;code = 105
char = n;code = 110
char = g;code = 103
char = ;code = 32
char = R;code = 82
char = N;code = 78
char = A;code = 65
char = ;code = 32
char = (;code = 40
char = s;code = 115
char = i;code = 105
char = R;code = 82
char = N;code = 78
char = A;code = 65
char = );code = 41
char = ;code = 32
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = M;code = 77
char = M;code = 77
char = P;code = 80
char = -;code = 45
char = 1;code = 49
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = M;code = 77
char = M;code = 77
char = P;code = 80
char = -;code = 45
char = 3;code = 51
char = ;code = 32
char = e;code = 101
char = x;code = 120
char = p;code = 112
char = r;code = 114
char = e;code = 101
char = s;code = 115
char = s;code = 115
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = h;code = 104
char = u;code = 117
char = m;code = 109
char = a;code = 97
char = n;code = 110
char = ;code = 32
char = d;code = 100
char = e;code = 101
char = r;code = 114
char = m;code = 109
char = a;code = 97
char = l;code = 108
char = ;code = 32
char = f;code = 102
char = i;code = 105
char = b;code = 98
char = r;code = 114
char = o;code = 111
char = b;code = 98
char = l;code = 108
char = a;code = 97
char = s;code = 115
char = t;code = 116
char = s;code = 115
char = .;code = 46
char = <;code = 60
char = b;code = 98
char = r;code = 114
char = /;code = 47
char = >;code = 62
char = <;code = 60
char = b;code = 98
char = r;code = 114
char = /;code = 47
char = >;code = 62
char = <;code = 60
char = b;code = 98
char = >;code = 62
char = R;code = 82
char = E;code = 69
char = S;code = 83
char = U;code = 85
char = L;code = 76
char = T;code = 84
char = S;code = 83
char = ;code = 32
char = :;code = 58
char = ;code = 32
char = <;code = 60
char = /;code = 47
char = b;code = 98
char = >;code = 62
char = T;code = 84
char = r;code = 114
char = e;code = 101
char = a;code = 97
char = t;code = 116
char = m;code = 109
char = e;code = 101
char = n;code = 110
char = t;code = 116
char = ;code = 32
char = w;code = 119
char = i;code = 105
char = t;code = 116
char = h;code = 104
char = ;code = 32
char = a;code = 97
char = ;code = 32
char = p;code = 112
char = o;code = 111
char = t;code = 116
char = e;code = 101
char = n;code = 110
char = t;code = 116
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = s;code = 115
char = e;code = 101
char = l;code = 108
char = e;code = 101
char = c;code = 99
char = t;code = 116
char = i;code = 105
char = v;code = 118
char = e;code = 101
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = h;code = 104
char = i;code = 105
char = b;code = 98
char = i;code = 105
char = t;code = 116
char = o;code = 111
char = r;code = 114
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = S;code = 83
char = I;code = 73
char = R;code = 82
char = T;code = 84
char = 1;code = 49
char = ,;code = 44
char = ;code = 32
char = E;code = 69
char = X;code = 88
char = -;code = 45
char = 5;code = 53
char = 2;code = 50
char = 7;code = 55
char = ,;code = 44
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = c;code = 99
char = r;code = 114
char = e;code = 101
char = a;code = 97
char = s;code = 115
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = b;code = 98
char = a;code = 97
char = s;code = 115
char = a;code = 97
char = l;code = 108
char = ;code = 32
char = e;code = 101
char = x;code = 120
char = p;code = 112
char = r;code = 114
char = e;code = 101
char = s;code = 115
char = s;code = 115
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = l;code = 108
char = e;code = 101
char = v;code = 118
char = e;code = 101
char = l;code = 108
char = s;code = 115
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = M;code = 77
char = M;code = 77
char = P;code = 80
char = -;code = 45
char = 1;code = 49
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = M;code = 77
char = M;code = 77
char = P;code = 80
char = -;code = 45
char = 3;code = 51
char = ;code = 32
char = p;code = 112
char = r;code = 114
char = o;code = 111
char = t;code = 116
char = e;code = 101
char = i;code = 105
char = n;code = 110
char = s;code = 115
char = .;code = 46
char = ;code = 32
char = K;code = 75
char = n;code = 110
char = o;code = 111
char = c;code = 99
char = k;code = 107
char = d;code = 100
char = o;code = 111
char = w;code = 119
char = n;code = 110
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = e;code = 101
char = n;code = 110
char = d;code = 100
char = o;code = 111
char = g;code = 103
char = e;code = 101
char = n;code = 110
char = o;code = 111
char = u;code = 117
char = s;code = 115
char = ;code = 32
char = S;code = 83
char = I;code = 73
char = R;code = 82
char = T;code = 84
char = 1;code = 49
char = ;code = 32
char = b;code = 98
char = y;code = 121
char = ;code = 32
char = s;code = 115
char = i;code = 105
char = R;code = 82
char = N;code = 78
char = A;code = 65
char = ;code = 32
char = l;code = 108
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = t;code = 116
char = o;code = 111
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = c;code = 99
char = r;code = 114
char = e;code = 101
char = a;code = 97
char = s;code = 115
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = e;code = 101
char = x;code = 120
char = p;code = 112
char = r;code = 114
char = e;code = 101
char = s;code = 115
char = s;code = 115
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = M;code = 77
char = M;code = 77
char = P;code = 80
char = -;code = 45
char = 1;code = 49
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = M;code = 77
char = M;code = 77
char = P;code = 80
char = -;code = 45
char = 3;code = 51
char = ;code = 32
char = a;code = 97
char = t;code = 116
char = ;code = 32
char = b;code = 98
char = o;code = 111
char = t;code = 116
char = h;code = 104
char = ;code = 32
char = m;code = 109
char = R;code = 82
char = N;code = 78
char = A;code = 65
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = p;code = 112
char = r;code = 114
char = o;code = 111
char = t;code = 116
char = e;code = 101
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = l;code = 108
char = e;code = 101
char = v;code = 118
char = e;code = 101
char = l;code = 108
char = s;code = 115
char = .;code = 46
char = ;code = 32
char = S;code = 83
char = I;code = 73
char = R;code = 82
char = T;code = 84
char = 1;code = 49
char = ;code = 32
char = k;code = 107
char = n;code = 110
char = o;code = 111
char = c;code = 99
char = k;code = 107
char = d;code = 100
char = o;code = 111
char = w;code = 119
char = n;code = 110
char = ;code = 32
char = a;code = 97
char = l;code = 108
char = s;code = 115
char = o;code = 111
char = ;code = 32
char = u;code = 117
char = p;code = 112
char = r;code = 114
char = e;code = 101
char = g;code = 103
char = u;code = 117
char = l;code = 108
char = a;code = 97
char = t;code = 116
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = M;code = 77
char = M;code = 77
char = P;code = 80
char = ;code = 32
char = p;code = 112
char = r;code = 114
char = o;code = 111
char = t;code = 116
char = e;code = 101
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = d;code = 100
char = u;code = 117
char = c;code = 99
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = c;code = 99
char = a;code = 97
char = u;code = 117
char = s;code = 115
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = b;code = 98
char = y;code = 121
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = f;code = 102
char = l;code = 108
char = a;code = 97
char = m;code = 109
char = m;code = 109
char = a;code = 97
char = t;code = 116
char = o;code = 111
char = r;code = 114
char = y;code = 121
char = ;code = 32
char = c;code = 99
char = y;code = 121
char = t;code = 116
char = o;code = 111
char = k;code = 107
char = i;code = 105
char = n;code = 110
char = e;code = 101
char = ,;code = 44
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = t;code = 116
char = e;code = 101
char = r;code = 114
char = l;code = 108
char = e;code = 101
char = u;code = 117
char = k;code = 107
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = (;code = 40
char = I;code = 73
char = L;code = 76
char = );code = 41
char = -;code = 45
char = 1;code = 49
char = &;code = 38
char = #;code = 35
char = 9;code = 57
char = 4;code = 52
char = 6;code = 54
char = ;;code = 59
char = .;code = 46
char = ;code = 32
char = M;code = 77
char = o;code = 111
char = r;code = 114
char = e;code = 101
char = o;code = 111
char = v;code = 118
char = e;code = 101
char = r;code = 114
char = ,;code = 44
char = ;code = 32
char = t;code = 116
char = r;code = 114
char = e;code = 101
char = a;code = 97
char = t;code = 116
char = m;code = 109
char = e;code = 101
char = n;code = 110
char = t;code = 116
char = ;code = 32
char = w;code = 119
char = i;code = 105
char = t;code = 116
char = h;code = 104
char = ;code = 32
char = a;code = 97
char = ;code = 32
char = S;code = 83
char = I;code = 73
char = R;code = 82
char = T;code = 84
char = 1;code = 49
char = ;code = 32
char = a;code = 97
char = c;code = 99
char = t;code = 116
char = i;code = 105
char = v;code = 118
char = a;code = 97
char = t;code = 116
char = o;code = 111
char = r;code = 114
char = ,;code = 44
char = ;code = 32
char = r;code = 114
char = e;code = 101
char = s;code = 115
char = v;code = 118
char = e;code = 101
char = r;code = 114
char = a;code = 97
char = t;code = 116
char = r;code = 114
char = o;code = 111
char = l;code = 108
char = ,;code = 44
char = ;code = 32
char = s;code = 115
char = i;code = 105
char = g;code = 103
char = n;code = 110
char = i;code = 105
char = f;code = 102
char = i;code = 105
char = c;code = 99
char = a;code = 97
char = n;code = 110
char = t;code = 116
char = l;code = 108
char = y;code = 121
char = ;code = 32
char = s;code = 115
char = u;code = 117
char = p;code = 112
char = p;code = 112
char = r;code = 114
char = e;code = 101
char = s;code = 115
char = s;code = 115
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = I;code = 73
char = L;code = 76
char = -;code = 45
char = 1;code = 49
char = &;code = 38
char = #;code = 35
char = 9;code = 57
char = 4;code = 52
char = 6;code = 54
char = ;;code = 59
char = -;code = 45
char = m;code = 109
char = e;code = 101
char = d;code = 100
char = i;code = 105
char = a;code = 97
char = t;code = 116
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = d;code = 100
char = u;code = 117
char = c;code = 99
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = M;code = 77
char = M;code = 77
char = P;code = 80
char = -;code = 45
char = 1;code = 49
char = ,;code = 44
char = ;code = 32
char = w;code = 119
char = h;code = 104
char = i;code = 105
char = c;code = 99
char = h;code = 104
char = ;code = 32
char = w;code = 119
char = a;code = 97
char = s;code = 115
char = ;code = 32
char = a;code = 97
char = t;code = 116
char = t;code = 116
char = e;code = 101
char = n;code = 110
char = u;code = 117
char = a;code = 97
char = t;code = 116
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = b;code = 98
char = y;code = 121
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char = p;code = 112
char = r;code = 114
char = e;code = 101
char = t;code = 116
char = r;code = 114
char = e;code = 101
char = a;code = 97
char = t;code = 116
char = m;code = 109
char = e;code = 101
char = n;code = 110
char = t;code = 116
char = ;code = 32
char = w;code = 119
char = i;code = 105
char = t;code = 116
char = h;code = 104
char = ;code = 32
char = E;code = 69
char = X;code = 88
char = -;code = 45
char = 5;code = 53
char = 2;code = 50
char = 7;code = 55
char = .;code = 46
char = ;code = 32
char = F;code = 70
char = i;code = 105
char = n;code = 110
char = a;code = 97
char = l;code = 108
char = l;code = 108
char = y;code = 121
char = ,;code = 44
char = ;code = 32
char = M;code = 77
char = M;code = 77
char = P;code = 80
char = -;code = 45
char = 1;code = 49
char = ;code = 32
char = p;code = 112
char = r;code = 114
char = o;code = 111
char = m;code = 109
char = o;code = 111
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char = e;code = 101
char = r;code = 114
char = ;code = 32
char = a;code = 97
char = c;code = 99
char = t;code = 116
char = i;code = 105
char = v;code = 118
char = i;code = 105
char = t;code = 116
char = y;code = 121
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char = w;code = 119
char = a;code = 97
char = s;code = 115
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char = i;code = 105
char = n;code = 110
char = c;code = 99
char = r;code = 114
char = e;code = 101
char = a;code = 97
char = s;code = 115
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = b;code = 98
char = y;code = 121
char = ;code = 32
char = E;code = 69
char = X;code = 88
char = -;code = 45
char = 5;code = 53
char = 2;code = 50
char = 7;code = 55
char = ;code = 32
char = i;code = 105
char = n;code = 110
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char = c;code = 99
char = e;code = 101
char = l;code = 108
char = l;code = 108
char = s;code = 115
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char = t;code = 116
char = r;code = 114
char = e;code = 101
char = a;code = 97
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char = e;code = 101
char = d;code = 100
char = ;code = 32
char = w;code = 119
char = i;code = 105
char = t;code = 116
char = h;code = 104
char = ;code = 32
char = o;code = 111
char = r;code = 114
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char = w;code = 119
char = i;code = 105
char = t;code = 116
char = h;code = 104
char = o;code = 111
char = u;code = 117
char = t;code = 116
char = ;code = 32
char = I;code = 73
char = L;code = 76
char = -;code = 45
char = 1;code = 49
char = &;code = 38
char = #;code = 35
char = 9;code = 57
char = 4;code = 52
char = 6;code = 54
char = ;;code = 59
char = .;code = 46
char = <;code = 60
char = b;code = 98
char = r;code = 114
char = /;code = 47
char = >;code = 62
char = <;code = 60
char = b;code = 98
char = r;code = 114
char = /;code = 47
char = >;code = 62
char = <;code = 60
char = b;code = 98
char = >;code = 62
char = C;code = 67
char = O;code = 79
char = N;code = 78
char = C;code = 67
char = L;code = 76
char = U;code = 85
char = S;code = 83
char = I;code = 73
char = O;code = 79
char = N;code = 78
char = S;code = 83
char = ;code = 32
char = :;code = 58
char = ;code = 32
char = <;code = 60
char = /;code = 47
char = b;code = 98
char = >;code = 62
char = O;code = 79
char = u;code = 117
char = r;code = 114
char = ;code = 32
char = f;code = 102
char = i;code = 105
char = n;code = 110
char = d;code = 100
char = i;code = 105
char = n;code = 110
char = g;code = 103
char = s;code = 115
char = ;code = 32
char = s;code = 115
char = u;code = 117
char = g;code = 103
char = g;code = 103
char = e;code = 101
char = s;code = 115
char = t;code = 116
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = a;code = 97
char = t;code = 116
char = ;code = 32
char = S;code = 83
char = I;code = 73
char = R;code = 82
char = T;code = 84
char = 1;code = 49
char = ;code = 32
char = e;code = 101
char = x;code = 120
char = e;code = 101
char = r;code = 114
char = t;code = 116
char = s;code = 115
char = ;code = 32
char = a;code = 97
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char = n;code = 110
char = e;code = 101
char = g;code = 103
char = a;code = 97
char = t;code = 116
char = i;code = 105
char = v;code = 118
char = e;code = 101
char = ;code = 32
char = r;code = 114
char = e;code = 101
char = g;code = 103
char = u;code = 117
char = l;code = 108
char = a;code = 97
char = t;code = 116
char = o;code = 111
char = r;code = 114
char = y;code = 121
char = ;code = 32
char = r;code = 114
char = o;code = 111
char = l;code = 108
char = e;code = 101
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = p;code = 112
char = r;code = 114
char = o;code = 111
char = d;code = 100
char = u;code = 117
char = c;code = 99
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = M;code = 77
char = M;code = 77
char = P;code = 80
char = -;code = 45
char = 1;code = 49
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = M;code = 77
char = M;code = 77
char = P;code = 80
char = -;code = 45
char = 3;code = 51
char = ;code = 32
char = i;code = 105
char = n;code = 110
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result sql = BACKGROUND : SIRT1, an NAD(+) -dependent histone/protein deacetylase, controls a broad range of cellular functions.
OBJECTIVES : We examined if SIRT1 is involved in the regulation of matrix metalloproteinase (MMP) expression in human dermal fibroblasts.
METHODS : We studied the effect of inhibition of SIRT1 by specific inhibitor and small interfering RNA (siRNA) on MMP-1 and MMP-3 expression in human dermal fibroblasts.
RESULTS : Treatment with a potent and selective inhibitor of SIRT1, EX-527, increased the basal expression levels of MMP-1 and MMP-3 proteins. Knockdown of endogenous SIRT1 by siRNA led to increased expression of MMP-1 and MMP-3 at both mRNA and protein levels. SIRT1 knockdown also upregulated MMP protein induction caused by an inflammatory cytokine, interleukin (IL)-1β. Moreover, treatment with a SIRT1 activator, resveratrol, significantly suppressed IL-1β-mediated induction of MMP-1, which was attenuated by pretreatment with EX-527. Finally, MMP-1 promoter activity was increased by EX-527 in cells treated with or without IL-1β.
CONCLUSIONS : Our findings suggest that SIRT1 exerts a negative regulatory role in the production of MMP-1 and MMP-3 in human dermal fibroblasts.
Publication: Br. J. Dermatol. 2010 Oct ;163(4)::689-94. :doi: 10.1111/j.1365-2133.2010.09825.x.
Publication Date: 2010 Oct
Study Author(s): Ohguchi, K;Itoh, T;Akao, Y;Inoue, H;Nozawa, Y;Ito, M;
Institution: Gifu International Institute of Biotechnology, 1-1 Naka-Fudogaoka, Kakamigahara, Gifu 504-0838, Japan. [email protected]
Shortcut link to this study:
Publication Date: 2010 Oct
Study Author(s): Ohguchi, K;Itoh, T;Akao, Y;Inoue, H;Nozawa, Y;Ito, M;
Institution: Gifu International Institute of Biotechnology, 1-1 Naka-Fudogaoka, Kakamigahara, Gifu 504-0838, Japan. [email protected]
Shortcut link to this study:
BACKGROUND : SIRT1, an NAD(+) -dependent histone/protein deacetylase, controls a broad range of cellular functions.
OBJECTIVES : We examined if SIRT1 is involved in the regulation of matrix metalloproteinase (MMP) expression in human dermal fibroblasts.
METHODS : We studied the effect of inhibition of SIRT1 by specific inhibitor and small interfering RNA (siRNA) on MMP-1 and MMP-3 expression in human dermal fibroblasts.
RESULTS : Treatment with a potent and selective inhibitor of SIRT1, EX-527, increased the basal expression levels of MMP-1 and MMP-3 proteins. Knockdown of endogenous SIRT1 by siRNA led to increased expression of MMP-1 and MMP-3 at both mRNA and protein levels. SIRT1 knockdown also upregulated MMP protein induction caused by an inflammatory cytokine, interleukin (IL)-1β. Moreover, treatment with a SIRT1 activator, resveratrol, significantly suppressed IL-1β-mediated induction of MMP-1, which was attenuated by pretreatment with EX-527. Finally, MMP-1 promoter activity was increased by EX-527 in cells treated with or without IL-1β.
CONCLUSIONS : Our findings suggest that SIRT1 exerts a negative regulatory role in the production of MMP-1 and MMP-3 in human dermal fibroblasts.
OBJECTIVES : We examined if SIRT1 is involved in the regulation of matrix metalloproteinase (MMP) expression in human dermal fibroblasts.
METHODS : We studied the effect of inhibition of SIRT1 by specific inhibitor and small interfering RNA (siRNA) on MMP-1 and MMP-3 expression in human dermal fibroblasts.
RESULTS : Treatment with a potent and selective inhibitor of SIRT1, EX-527, increased the basal expression levels of MMP-1 and MMP-3 proteins. Knockdown of endogenous SIRT1 by siRNA led to increased expression of MMP-1 and MMP-3 at both mRNA and protein levels. SIRT1 knockdown also upregulated MMP protein induction caused by an inflammatory cytokine, interleukin (IL)-1β. Moreover, treatment with a SIRT1 activator, resveratrol, significantly suppressed IL-1β-mediated induction of MMP-1, which was attenuated by pretreatment with EX-527. Finally, MMP-1 promoter activity was increased by EX-527 in cells treated with or without IL-1β.
CONCLUSIONS : Our findings suggest that SIRT1 exerts a negative regulatory role in the production of MMP-1 and MMP-3 in human dermal fibroblasts.
PMID: 20426787
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