Maturation of Growth Differentiation Factor 15 in Human Placental Trophoblast Cells Depends on the Interaction With Matrix Metalloproteinase-26

Context: Matrix Metalloproteinase-26 (MMP-26) is the smallest member of matrix metalloproteinase (MMP) family that functions mainly in the extracellular milieu to cleave the extracellular matrix proteins. It is expressed in various cell types of placenta, but its function in placentation has been poorly understood. Considering the existence of a unique cysteine switch sequence in MMP-26 protein sequence, as well as the evidence in cancer cells indicating the digestion of the NH2-terminal domain of ERβ by MMP-26, we hypothesize that MMP-26 may have specific intracellular activity in human placental trophoblast cells. Objective: This study aimed to identify the intracellular binding partners of MMP-26 and investigate how MMP-26 is involved in placentation through the interactions with its partners. Setting and Design: Yeast two-hybrid system was employed to screen potential binding partners of MMP-26 in human placenta. Immunoprecipitation and immunofluorescence assays were conducted to verify the interactio...