Tissue inhibitor of metalloproteinases 1 (TIMP-1) displays cytokine-like functions

rhTIMP-1 affects in vitro cell survival, proliferation, and particularly clonogenic expansion of CD34⁺ HSPCs without compromising their short-term engraftment potential after transplantation into immunodeficient mice

These effects are independent of matrix metalloproteinase (MMP) inhibition and rely on TIMP-1 binding to CD63

rhTIMP-1 stimulation induces PI3K recruitment and Akt phosphorylation, both presiding over survival/proliferation pathways in HSPCs, and increases CycD1 levels

rhTIMP-1 promotes clonogenic expansion and survival in human progenitors via the activation of the CD63/PI3K/pAkt signaling pathway, suggesting that TIMP-1 might be a key player in the network of proinflammatory factors modulating HSPC functions