Transient Receptor Potential Vanilloid 6 (TRPV6) Proteins Control the Extracellular Matrix Structure of the Placental Labyrinth

International Journal of Molecular Sciences

Claudia Fecher-Trost¹  Ulrich Wissenbach¹  Manuel Winter¹  Petra Weissgerber¹  Daniela Yildiz¹  StephanE. Philipp¹  Veit Flockerzi¹  Karolin Klein¹  MarkusR. Meyer¹  Femke Lux¹ 

[1] Experimental and Clinical Pharmacology and Toxicology, Center for Molecular Signaling (PZMS), Saarland University, Buildings 61.4 and 46, 66421 Homburg, Germany;

关键词: TRPV6;    calcium homeostasis;    trophoblast;    extracellular matrix;    placenta;    fibronectin;   

DOI  :  10.3390/ijms21249674

来源: DOAJ

【 摘 要 】

Calcium-selective transient receptor potential Vanilloid 6 (TRPV6) channels are expressed in fetal labyrinth trophoblasts as part of the feto–maternal barrier, necessary for sufficient calcium supply, embryo growth, and bone development during pregnancy. Recently, we have shown a less- compact labyrinth morphology of Trpv6-deficient placentae, and reduced Ca²⁺ uptake of primary trophoblasts upon functional deletion of TRPV6. Trpv6^-/- trophoblasts show a distinct calcium-dependent phenotype. Deep proteomic profiling of wt and Trpv6^-/- primary trophoblasts using label-free quantitative mass spectrometry leads to the identification of 2778 proteins. Among those, a group of proteases, including high-temperature requirement A serine peptidase 1 (HTRA1) and different granzymes are more abundantly expressed in Trpv6^-/- trophoblast lysates, whereas the extracellular matrix protein fibronectin and the fibronectin-domain-containing protein 3A (FND3A) were markedly reduced. Trpv6^-/-placenta lysates contain a higher intrinsic proteolytic activity increasing fibronectin degradation. Our results show that the extracellular matrix formation of the placental labyrinth depends on TRPV6; its deletion in trophoblasts correlates with the increased expression of proteases controlling the extracellular matrix in the labyrinth during pregnancy.

【 授权许可】

Unknown