Notch signal deficiency alleviates hypertrophic scar formation after wound healing through the inhibition of inflammation.

Pathological scar is a common complication after wound healing. One of the most important factors that affects scar formation is inflammation. During this process, macrophages play a critical role in the wound healing process, as well as in scar formation. Notch signaling is reported to participate in inflammation and fibrosis; however, whether it affects scar formation is still unclear. In this study, RBP-J knockout mice, in which Notch signaling was down-regulated, and control mice were used, and a skin incision model was established. Sirius red staining and Masson staining suggested that RBP-J knockout could significantly reduce collagen sedimentation after wound healing. Western blot analysis and RT-PCR also confirmed the results. During wound healing, the expression of inflammatory cytokines and macrophage infiltration were decreased in RBP-J knockout mice. In vitro, it was also verified that RBP-J deficiency in macrophages effectively suppressed the expression of inflammatory cytokines and chemotaxis of macrophages after LPS stimulation. In conclusion, blocking Notch signaling in macrophages effectively alleviated scar formation by suppressing the inflammatory response and collagen sedimentation.

MicroRNA-494 targets PTEN and suppresses PI3K/AKT pathway to alleviate hypertrophic scar formation.

Hypertrophic scar is a common complication after skin injury. MicroRNAs have been reported related to hypertrophic scar through posttranscriptional control of genes. Hypertrophic scar-derived fibroblast model and mice incision model were used to see the expression of microRNA-494 and whether the level changes of microRNA-494 could affect scar formation. It was found that in hypertrophic scar, the expression of microRNA-494 decreased. However, after over-express microRNA-494 in fibroblasts, the levels of scar related molecules such as Col I, Col III increased. And when suppress the level of microRNA-494 in fibroblasts, the levels of collagen decreased. Moreover, the up-regulation of microRNA-494 led to decreased apoptosis of fibroblasts while the down-regulation of it led to increased apoptosis. Further, it was found that PTEN was one of the downstream targets of microRNA-494. The up-regulation of PTEN led to inactivation of PI3K/AKT pathway and the decreased expression of collagens. In conclusion, we confirmed that microRNA-494 could be a key regulator to suppress hypertrophic scar formation. The suppression of microRNA-494 could eliminate its inhibition effect to PTEN and finally decrease the expression of collagen and inhibit hypertrophic scar formation.