| First Author | Rossi L | Year | 2011 |
| Journal | Blood | Volume | 117 |
| Issue | 24 | Pages | 6479-88 |
| PubMed ID | 21521782 | Mgi Jnum | J:174818 |
| Mgi Id | MGI:5141203 | Doi | 10.1182/blood-2009-10-248955 |
| Citation | Rossi L, et al. (2011) TIMP-1 deficiency subverts cell-cycle dynamics in murine long-term HSCs. Blood 117(24):6479-88 |
| abstractText | In addition to the well-recognized role in extracellular matrix remodeling, the tissue inhibitor of metalloproteinases-1 (TIMP-1) has been suggested to be involved in the regulation of numerous biologic functions, including cell proliferation and survival. We therefore hypothesized that TIMP-1 might be involved in the homeostatic regulation of HSCs, whose biologic behavior is the synthesis of both microenvironmental and intrinsic cues. We found that TIMP-1(-/-) mice have decreased BM cellularity and, consistent with this finding, TIMP-1(-/-) HSCs display reduced capability of long-term repopulation. Interestingly, the cell cycle distribution of TIMP-1(-/-) stem cells appears distorted, with a dysregulation at the level of the G(1) phase. TIMP-1(-/-) HSCs also display increased levels of p57, p21, and p53, suggesting that TIMP-1 could be intrinsically involved in the regulation of HSC cycling dynamics. Of note, TIMP-1(-/-) HSCs present decreased levels of CD44 glycoprotein, whose expression has been proven to be controlled by p53, the master regulator of the G(1)/S transition. Our findings establish a role for TIMP-1 in regulating HSC function, suggesting a novel mechanism presiding over stem cell quiescence in the framework of the BM milieu. |
