Effect of metalloproteinase-2 on expression of tissue inhibitor of matrix metalloproteinase-4 in cutaneous wound healing in balb/c mice

Document Type: Original Article

Authors

1 Oral and maxillofacial pathology, Dental faculty, Shahid beheshti university of medical science, Tehran, Iran

2 Oral and maxillofacial pathology, Dental faculty, Shahid beheshti university of medical science,Tehran, Iran.

3 Biochemistry department, Pasteur institute of Iran,Tehran, Iran.

10.22034/jbr.2020.223176.1020

Abstract

Introduction: Wound healing comprised serial phases. Though the insitu factors activate to rehabilitate properly immediately after wounding, it eventuate in scar frequently. Collagenases and their inhibitors have dramatic role in processes which prevents scaring.
Objective: We inject “TIMP-4” in cutaneous wound in BALB/C mice to block MMP-2 and search for consequence.
Methods: MMP-2 antibody was injected in dorsal skin of 6-8 weeks BALB/C mice at the level of scapula, on certain periods (4houres, 3 days, 7 days and 14 days after wounding)we collect tissue specimens from dorsal skin of mice using 3mm punch biopsy. We cloned CDNA of MMP-2 and TIMP-4 ,then investigate the expression of genes (using quantitative real time RT-PCR and IHC). The results were analyzed in Wilcoxon Signed Ranks Test, Kruskal-Wallis and Dunn (SPSS version PASW Statistics 18). 
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Results: Four hours after wounding RNA copies and enzymes of MMP-2 increased with lower inflammation in treated samples, RNA copies and enzyme of TIMP-4 was almost similar in the first stage. Three days after injury RNA copies of MMP-2 and TIMP-4 increased and epithelial reattachment was lower in treated group. TIMP-4 enzymes and inflammation rised in third group, the number of RNA copies of TIMP-4 did not change, but the number of RNA copies of MMP-2 decreased in treated samples. Although forth treated group shows lower RNA copies of TIMP-4, the number of RNA copies of MMP-2 increased.
Conclusion: This study indicates that immunotherapy by MMP-2 antibody can lead to regeneration and scar reduction with lower TIMP-4 enzymes.

Graphical Abstract

Effect of metalloproteinase-2 on expression of tissue inhibitor of matrix metalloproteinase-4 in cutaneous wound healing in balb/c mice

Keywords