Figure 1

The possible signaling pathways of EPCs senescence. In diabetes, HG and/or IR might induce EPCs senesecne via the following pathways. HG and/or IR could inhibit the PI3K-Akt-eNOS pathway, resulting in the decrease of NO, which might induce the EPCs senescence. At the same time, HG and/or IR could be a kind of ROS and induce senescence through the classical p16 and p53 dependent senescence pathway, in which p38 is also invovled. Moreover, we conjecture that HG and/or IR could activate the insulin receptor mediated Ras-MEK-RSK4 pathway, resulting in on one hand the EPCs senescence mediated by RSK4 via p21 signaling pathway and a more production of glucose on the other hand. In additon, RSK4 could be a cadidate gene for HNF4α, which activates p21 and thus inhibit the cell proliferation in diabetes. HG: high glucose; IR: insulin resistance; ROS: reactive oxygen species; GSK: glucose synthesis kinase; HNF4α: hepatic necrotic factor 4α.