Decellularized amniotic membrane promotes the anti-inflammatory response of macrophages via PI3K/AKT/HIF-1α pathway

Macrophages undergo dynamic transitions between M1 and M2 states, exerting profound influences on both inflammatory and regenerative processes. The biocompatible and wound-healing properties of decellularized amniotic membrane(d AM) make it a subject of exploration for its potential impact on the anti-inflammatory response of macrophages. Experimental findings unequivocally demonstrate that d AM promotes anti-inflammatory M2 polarization of macrophage, with its cytokine-rich content posited as a potential mediator. The application of RNA sequencing unveils differential gene expression, implicating the hypoxia inducible factor-1α(HIF-1α) signaling pathway in this intricate interplay. Subsequent investigation further demonstrates that d AM facilitates anti-inflammatory M2 polarization of macrophage through the upregulation of epidermal growth factor(EGF), which, in turn, activates the phosphatidylinositol 3-kinase(PI3K)/protein kinase B(AKT) pathway and stabilizes HIF-1α. This cascade results in a noteworthy augmentation of anti-inflammatory gene expression. This study significantly contributes to advancing our comprehension of d AM's immunomodulatory role in tissue repair, thereby suggesting promising therapeutic potential.