Title | The effects of DNA methyltransferase inhibitors and histone deacetylase inhibitors on digit regeneration in mice. |
Publication Type | Journal Article |
Year of Publication | 2010 |
Authors | Wang G, Badylak SF, Heber-Katz E, Braunhut SJ, Gudas LJ |
Journal | Regen Med |
Volume | 5 |
Issue | 2 |
Pagination | 201-20 |
Date Published | 2010 Mar |
ISSN | 1746-076X |
Keywords | Amputation, 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. |
DOI | 10.2217/rme.09.91 |
Alternate Journal | Regen Med |
PubMed ID | 20210581 |