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

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Nov 30, 2023 185 likes •517 views

MMPs 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

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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

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

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

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

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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

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

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Repair

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

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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 Type IV Collagenase 3.4.24.24 72 66 Denatured collagens, collagens IV, V, 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 Type IV Collagenase 3.4.24.35 92 86 Denatured collagens, collagens IV, V, 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 metalloelastase 3.4.24.65 54 22 Elastin, gelatin, collagen IV, fibronectin, laminin, vitronectin, proteoglycan MMP-13 Collagenase 3

48 Fibrillar collagens, gelatin, aggrecan

Matrix Metalloproteinases and their Substrates

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

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Remodeling

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

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

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

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1 10 100 nM SNAP 1 2 3 4 5 Relative Expression/18S rRNA

Effect of SNAP on MMP-9 Expression

Day 1

* * * * *

Contro Diabetic . 1 3 7 . Day 5000 10000 15000 20000 Cell Number Effect of SNAP on Cell Number

Control Control + SNAP Diabetic Diabetic + SNAP

Effect of Nitric Oxide Donor SNAP on Human Skin Fibroblasts

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Effect of Nitric Oxide Donors on MMP-9 Expression

1 3 7 Day 1 2 3 4 5 Relative Expression/18S rRNA

E ffect of S N O G on M M P -9 E xpress * * * * * *

C ontro C ontrol + SN OG D iabetic D iabetic + S N O G

1 3 7 Day 1 2 3 4 5 Relative Expression/18S rRNA

Effect of SNAP on MM P-9 Expressio * * * * * *

Contro Control + SNAP Diabetic Diabetic + SNAP

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1 3 7 Day 1 2 3 4 5 Relative Expression/18S rRNA

Effect of SNOG on MMP-8 Expression * * * * * *

Contro Control + SNOG Diabetic Diabetic + SNOG

1 3 7 Day 1 2 3 4 5 Relative Expression/18S rRNA

Effect of SNAP on MMP-8 Expression * * * * * *

Contro Control + SNAP Diabetic Diabetic + SNAP

Effect of Nitric Oxide Donors on MMP-8 Expression

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. 1 2 3 4 5 6 . W eeks 20 40 60 80 100 % Decrease in Wound Area Effect of Nitric O xide on W ound Healing

C ontrol D iabetic C ontrol + SNAP D iabetic + SN AP

. 1 2 3 4 5 6 . Weeks 20 40 60 80 100 % Decrease in Wound Area Effect of SNOG on Wound Healing

Control Diabetic Control + SNOG Diabetic + SNOG

Effect of Nitric Oxide Donors on Wound Healing

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Questions?

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