Fig. 4:

The proposed mechanism for IH formation in the abdominal wall: The incision triggers classical inflammatory responses where the persistence of inflammation induces the ECM damage by decreasing the ratio of collagen type 1 to type 3. This is due to the hyperactivity of MMPs and inhibition of TIMPs. The inflammation and ECM damage triggers the expression and activation of TGF-β1 which reduces inflammation by increasing the ratio of collagen type 1 to type 3, and inhibition of MMPs by TIMP activation. TGF-β1 modulates the transdifferentiation of fibroblasts to myofibroblasts by upregulating α-SMA and collagen type 1. TGF-β1 also activates CTGF and LOX, which induces the transdifferentiation of fibroblasts to myofibroblasts. The wound stress and HIF-1α trigger LOX activity which functions in collagen maturation. The HMGB1 triggers inflammation via the activation of inflammasome. The high ratio of TGF-β1-to-HMGB1 drives TGF-β1 signaling to trigger healing responses, whereas the low ratio results in delayed healing by the persistence of inflammation that leads to the formation of incisional hernia.