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

Abstract

This is the first report to demonstrate the physiological function of placental MMP-26 in processing GDF15 and subsequently promoting trophoblast cell apoptosis. These findings expand our understanding of the working mechanism of the metalloproteinase in the process of placentation.

Mechanically-induced GDF15 Secretion by Periodontal Ligament Fibroblasts Regulates Osteogenic Transcription

“…We also detected significantly higher GDF15 levels in the media of stretched PdLF compared to unstressed controls. Beside the release of matured GDF15 protein, GDF15 is partially secreted as unprocessed propeptide bound to ECM components 25 and extracellular N-terminal cleavage by the matrix metalloproteinases (MMP) produce the active form of the GDF15 protein 39,40 . Following orthodontic treatment, we also detected increased staining of GDF15 in the ECM of rat jaw tissue.…”

Presence of growth/differentiation factor-15 cytokine in human follicular fluid, granulosa cells, and oocytes

“…GDF-15 is synthesized as an inactive precursor that is dimerized in the endoplasmic reticulum, then transported to the Golgi apparatus for proteolytic cleavage by furin-like proteases, and eventual secretion as an active dimer [28]. However, certain cells secrete large pools of unprocessed GDF-15 that subsequently inhabit the extracellular matrix, perhaps undergoing processing via extracellular MMP-26 [16,41]. Preprocessed and/or mature GDF-15 forms have been suggested to be differentially deposited in extracellular matrix [16].…”

Diabetes mellitus related biomarker: The predictive role of growth-differentiation factor-15

“…Inversely, GDF15 probably is able to bind with matrix metalloproteinase 26 that facilitate the pro-apoptotic effect of this cytokine [20].…”