MMPs and Their Role in the Wound Victor L. Sylvia, Ph.D. Associate - PowerPoint PPT Presentation

MMP’s and Their Role in the Wound Victor L. Sylvia, Ph.D. Associate Professor Department of Orthopaedics University of Texas Health Science Center 7703 Floyd Curl Drive San Antonio, TX 78220

http://www.med.ufl.edu/IDP/Core/Section%205/IDP%20Grand%20Rounds%20Tissue%20Engineering%202005%20version%203%20compressed.pdf

http://www.med.ufl.edu/IDP/Core/Section%205/IDP%20Grand%20Rounds%20Tissue%20Engineering%202005%20version%203%20compressed.pdf

http://www.med.ufl.edu/IDP/Core/Section%205/IDP%20Grand%20Rounds%20Tissue%20Engineering%202005%20version%203%20compressed.pdf

MMPs and Growth Factors • Pathological dysregulation of MMP activity results in excessive breakdown of the extracellular matrix (ECM) and loss of growth factors , involved in normal healing, that are stored in the ECM. • Growth factors such as PDGF-BB, TGF- β and VEGF are found in decreased amounts in chronic wounds, presumably due to the increase in MMPs (Loot et al., 2002; Lerman et al., 2003; Robson et al., 2004) .

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http://www.med.ufl.edu/IDP/Core/Section%205/IDP%20Grand%20Rounds%20Tissue%20Engineering%202005%20version%203%20compressed.pdf

Repair

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Matrix Metalloproteinases and their Substrates MMP Synonyms EC Classification Latent M.W. (kDa) Active M.W. (kDa) Substrates MMP-1 Interstitial Collagenase 3.4.24.7 55 45 Fibrillar collagens, casein, gelatin, proteoglycan MMP-2 Gelatinase A, 72 kDa 3.4.24.24 72 66 Denatured collagens, Type IV collagens IV, V, Collagenase VII, X, gelatin MMP-3 Stromelysin-1 3.4.24.17 57 45 Proteoglycan, collagens X, XI, procollagens, gelatin, laminin, collagenase, gelatinase B MMP-7 Matrilysin ; PUMP 3.4.24.23 28 19 As stromelysin 1, elastin MMP-8 Neutrophil collagenase 3.4.24.34 75 58 Fibrillar collagens, gelatin, proteoglycan MMP-9 Gelatinase B, 92 kDa 3.4.24.35 92 86 Denatured collagens, Type IV collagens IV, V, Collagenase VII, X MMP-10 Stromelysin 2 3.4.24.22 57 44 As Stromelysin 1 MMP-11 Stromelysin 3 62 47 Unknown MMP-12 Macrophage 3.4.24.65 54 22 Elastin, gelatin, metalloelastase collagen IV, fibronectin, laminin, vitronectin, proteoglycan MMP-13 Collagenase 3 -- 66 48 Fibrillar collagens, gelatin, aggrecan

http://www.med.ufl.edu/IDP/Core/Section%205/IDP%20Grand%20Rounds%20Tissue%20Engineering%202005%20version%203%20compressed.pdf

Remodeling

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http://www.med.ufl.edu/IDP/Core/Section%205/IDP%20Grand%20Rounds%20Tissue%20Engineering%202005%20version%203%20compressed.pdf

Effect of Nitric Oxide Donor SNAP on Human Skin Fibroblasts Effect of SNAP on MMP-9 Expression Effect of SNAP on Cell Number Day 1 20000 5 Control Contro Relative Expression/18S rRNA Control + SNAP 4 Diabetic 15000 Diabetic Diabetic + SNAP * Cell Number 3 10000 2 * 5000 * 1 * * 0 0 . 1 3 7 . 0 1 10 100 Day nM SNAP

Effect of Nitric Oxide Donors on MMP-9 Expression E ffect of S N O G on M M P -9 E xpress Effect of SNAP on MM P-9 Expressio 5 5 Contro C ontro Relative Expression/18S rRNA Control + SNAP Relative Expression/18S rRNA C ontrol + SN OG 4 4 Diabetic D iabetic Diabetic + SNAP D iabetic + S N O G 3 3 2 2 * * 1 1 * * * * * * * * * * 0 0 1 3 7 1 3 7 Day Day

Effect of Nitric Oxide Donors on MMP-8 Expression Effect of SNAP on MMP-8 Expression Effect of SNOG on MMP-8 Expression 5 5 Contro Contro Relative Expression/18S rRNA Relative Expression/18S rRNA Control + SNAP Control + SNOG 4 4 Diabetic Diabetic Diabetic + SNOG Diabetic + SNAP 3 3 2 2 * * 1 1 * * * * * * * * * * 0 0 1 3 7 1 3 7 Day Day

Effect of Nitric Oxide Donors on Wound Healing Effect of Nitric O xide on W ound Healing Effect of SNOG on Wound Healing C ontrol Control 100 100 % Decrease in Wound Area % Decrease in Wound Area D iabetic Diabetic C ontrol + SNAP Control + SNOG 80 80 D iabetic + SN AP Diabetic + SNOG 60 60 40 40 20 20 0 0 . 1 2 3 4 5 6 . . 1 2 3 4 5 6 . W eeks Weeks

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