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Alpha V integrin prolongs collagenase production through Jun activation binding protein 1
Howard Levinson1, Alok K Sil, John E Conwell
1Division of Plastic Surgery, M.S. Hershey Medical Center, Hershey, PA, USA. hlev1@yahoo.com
Annals of Plastic Surgery
|July 23, 2004
Summary
Alpha-v integrin and matrix metalloproteinase 1 (MMP1) are key in cancer and healing. This study shows alpha-v integrin signals via JAB1 to boost MMP1, potentially causing abnormal scarring.
Area of Science:
- Cell Biology
- Biochemistry
- Dermatology
Background:
- Alpha-v integrin and matrix metalloproteinase 1 (MMP1) are crucial in cancer metastasis and wound healing.
- Abnormal scarring is associated with fibroblast overexpression of alpha-v integrin.
- The relationship between alpha-v integrin expression and MMP1 production requires elucidation.
Purpose of the Study:
- To investigate the interaction between alpha-v integrin and JAB1.
- To determine the role of alpha-v integrin in MMP1 production.
- To explore the signaling pathway linking alpha-v integrin, JAB1, and MMP1 in fibroblasts.
Main Methods:
- Yeast two-hybrid screening to identify interacting proteins.
- Transfection of mesenchymal-derived cells with alpha-v integrin gene.
- Collagen lattice contraction assays.
- Luciferase assays to measure MMP1 transcription.
- JAB1 antisense to inhibit JAB1 expression.
Main Results:
- Alpha-v integrin interacts with JAB1.
- Alpha-v integrin-transfected cells exhibited enhanced collagen lattice contraction.
- Late-phase contraction was inhibited by a pan-MMP inhibitor (BB4).
- Overexpression of alpha-v integrin correlated with enhanced MMP1 transcription (P < 0.05).
- JAB1 diminution abolished alpha-v integrin-induced MMP1 up-regulation.
Conclusions:
- Alpha-v integrin signals through JAB1 to prolong MMP1 production.
- This signaling pathway in fibroblasts may contribute to abnormal scarring.
- Targeting this pathway could offer therapeutic strategies for scar management.