Possible important roles of galectins in the healing of human fetal membranes

Abstract

The fetal membranes healing is a complex and dynamic process of replacing devitalized and missing cellular structures and tissue layers. Multiple cells and extracellular matrices, and cell differentiation, migration and proliferation may participate in restoring the integrity of damaged tissue, however this process still remains unclear. Therefore, there is a need to identify and integrate new ideas and methods to design a more effective dressing to accelerate fetal membrane healing. This review explores the function and role of galectins in the inflammatory, epithelial mesenchymal transition, proliferative migration, and remodeling phases of fetal membrane healing. In conclusion, the preliminary findings are promising. Research on amnion regeneration is expected to provide insight into potential treatment strategies for premature rupture of membranes.

Keywords: amniotic epithelial cells; amniotic mesenchymal cells; fetal membrane; galectin; macrophages; wound healing.

Figure 1

Inflammatory phase of fetal/amnion membrane healing. The inflammatory response caused by fetal membrane injury provides the possibility to initiate the healing of fetal membranes. (A) The fetal membranes are ruptured by external infection or mechanical injury; (B) Monocytes are first recruited from amniotic fluid to the site of injury and transformed into macrophages; (C) Galectins stimulate monocytes to enhance the expression levels of Akt, PI3K and PPAR-γ, and turn on the M2 polarization of macrophages; (D) M2-type macrophages release TNF-α, IL-1β and other cytokines to promote fetal membrane healing. M2-type macrophages release cytokines such as TNF-α and IL-1β to promote the healing of amnion membranes. akt, protein kinase B; PI3K, phosphatidylinositol-3 kinase; PPAR-γ, peroxisome proliferator-activated receptor-gamma; TNF-α, tumor necrosis factor-α; IL- 1β, interleukin-1β.

Figure 2

Epithelial-mesenchymal transition phase of fetal/amnion membrane healing. Expression of inflammatory factors after amnion membrane rupture can promote epithelial- mesenchymal transition, and EMT can accelerate cell migration, thus accelerating wound closure. (A–C) Galectins stimulate amnion epithelial cells through the Hedgehog signal pathway, TGF-β1/Smad signal pathway, MAPK JNK/p38 signal pathway, FAK / PI3K / AKT / mTOR signal pathway and NF-κB signal pathway stimulated the transformation of amnion epithelial cells into amnion mesenchymal cells. EMT, epithelial-mesenchymal transition.

Figure 3

Migratory proliferative phase of fetal/amnion membrane healing. (A, B) Galectins regulate cells migration by interacting with MMPs; (C, D) Galectins regulate cells proliferation by interacting with EGF, TGF-β1, HGF, bFGF and other proteins. Abbreviations: EMT, epithelial-mesenchymal transition; MMPs, matrix metalloproteinases; EGF, epidermal growth factor ; TGF-β1, transforming growth-factor-β1; HGF, hepatocyte growth factor; bFGF, basic fibroblast growth factor.