The effects of DNA methyltransferase inhibitors and histone deacetylase inhibitors on digit regeneration in mice.

TitleThe effects of DNA methyltransferase inhibitors and histone deacetylase inhibitors on digit regeneration in mice.
Publication TypeJournal Article
Year of Publication2010
AuthorsWang G, Badylak SF, Heber-Katz E, Braunhut SJ, Gudas LJ
JournalRegen Med
Volume5
Issue2
Pagination201-20
Date Published2010 Mar
ISSN1746-076X
KeywordsAmputation, Animals, Azacitidine, Female, Forelimb, Gene Expression Regulation, Histone Deacetylase Inhibitors, Hydroxamic Acids, Methyltransferases, Mice, Mice, Inbred C57BL, Proliferating Cell Nuclear Antigen, Regeneration, RNA, Messenger, Staining and Labeling, Toes
Abstract

METHOD: We injected two drugs that modify the epigenome, the DNA methyltransferase inhibitor 5-aza-2'-deoxycytidine (5-aza-dC) and the histone deacetylase inhibitor trichostatin A (TSA), alone or in combination, into C57Bl/6 mice subjected to amputation through the mid-second phalanx of the third digit. Wound-site tissue was collected.

RESULTS: We observed increased staining of the stem cell markers Rex1 (Zfp42) and stem cell antigen-1 at digit amputation sites from drug-treated mice. Samples from 5-aza-dC plus TSA and TSA treated mice also showed increased proliferating cell nuclear antigen staining, a measure of cell proliferation. Drug treatments increased Msx1, but not Cyp26a1 or ALDH1a2 (RALDH2) mRNA.

CONCLUSION: 5-aza-dC and TSA treatments stimulated cell proliferation at the amputation site, possibly via increased expression of genes involved in digit development and regeneration.

DOI10.2217/rme.09.91
Alternate JournalRegen Med
PubMed ID20210581