Expression and organization of basement membranes and focal adhesion proteins in pregnant myometrium is regulated by uterine stretch.
The mechanisms underlying the preparation of the uterus for labor are not fully understood. We have previously found a significant increase in the expression of messenger RNA (mRNAs) encoding extracellular basement membrane (BM) proteins of the smooth muscle cells (SMCs) in late pregnant rat myometrium. At term, the myometrium is stretched by growing fetuses and these mechanical signals are transmitted from extracellular matrix into SMCs through focal adhesions (FA). The aim of this study was to investigate the effect of gravidity on the expression and spatiotemporal distribution of major BM proteins, laminin-gamma2 and collagen IV, as well as typical FA constituents, vinculin and paxillin, in the myometrium during gestation and parturition, using a unilaterally pregnant rat model. We found that the expression of laminin-gamma2 and collagen IV proteins increased significantly with gestational age (P < .05) and was dependent on gravidity whereas vinculin and paxillin proteins were not affected. Near term, BM proteins from gravid horn myometrium demonstrated increased extracellular immunostaining and major rearrangement from sporadic protein distribution to organized, continuous, and regular structures surrounding the plasma membrane of each myocyte. Examination of FA proteins revealed that paxillin was translocated from the cytoplasm to the cell periphery, while vinculin was sequestered specifically to FAs. At labor, BM and FA proteins, organized in similar bead-like structures, were localized on opposing sides of SMC plasma membrane into 2 different compartments. We suggest that these stretch-induced changes facilitate formation of stable cell-matrix adhesions and provide the molecular basis for optimal force transduction during labor contractions.
Shynlova
Oksana
O
Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada, M5T 3H7. shynlova@lunenfeld.ca
Chow
Michelle
M
Lye
Stephen J
SJ
D000818:Animals; D001485:Basement Membrane / Q000166:cytology / Q000502:physiology*; D024141:Collagen Type IV / Q000096:biosynthesis; D016326:Extracellular Matrix Proteins / Q000096:biosynthesis*; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D007797:Laminin / Q000096:biosynthesis; D009215:Myometrium / Q000166:cytology / Q000378:metabolism* / Q000502:physiology; D051419:Paxillin / Q000096:biosynthesis; D011247:Pregnancy; D011257:Pregnancy Proteins / Q000096:biosynthesis*; D051381:Rats; D017208:Rats, Wistar; D014590:Uterine Contraction / Q000502:physiology*; D014599:Uterus / Q000166:cytology / Q000378:metabolism / Q000502:physiology; D016596:Vinculin / Q000096:biosynthesis
D024141:Collagen Type IV; D016326:Extracellular Matrix Proteins; D007797:Laminin; D051419:Paxillin; D011257:Pregnancy Proteins; D016596:Vinculin