Increased phosphorylation of myosin light chain prevents in vitro decidualization.
Differentiation of stromal cells into decidual cells, which is critical to successful pregnancy, represents a complex transformation requiring changes in cytoskeletal architecture. We demonstrate that in vitro differentiation of human uterine fibroblasts into decidual cells includes down-regulation of alpha-smooth muscle actin and beta-tubulin, phosphorylation of focal adhesion kinase, and redistribution of vinculin. This is accompanied by varied adhesion to fibronectin and a modified ability to migrate. Cytoskeletal organization is determined primarily by actin-myosin II interactions governed by the phosphorylation of myosin light chain (MLC20). Decidualization induced by cAMP [with estradiol-17beta (E) and medroxyprogesterone acetate (P)] results in a 40% decrease in MLC20 phosphorylation and a 55% decline in the long (214 kDa) form of myosin light-chain kinase (MLCK). Destabilization of the cytoskeleton by inhibitors of MLCK (ML-7) or myosin II ATPase (blebbistatin) accelerates decidualization induced by cAMP (with E and P) but inhibits decidualization induced by IL-1beta (with E and P). Adenoviral infection of human uterine fibroblast cells with a constitutively active form of MLCK followed by decidualization stimuli leads to a 30% increase in MLC20 phosphorylation and prevents decidualization. These data provide evidence that the regulation of cytoskeletal dynamics by MLC20 phosphorylation is critical for decidualization.
Ihnatovych
Ivanna
I
Department of Obstetrics and Gynecology, The University of Illinois at Chicago, 820 South Wood Street (M/C 808), Chicago, Illinois 60612-7313, USA.
Hu
WenYang
W
Martin
Jody L
JL
Fazleabas
Asgerally T
AT
de Lanerolle
Primal
P
Strakova
Zuzana
Z
D000199:Actins / Q000378:metabolism; D002448:Cell Adhesion / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000494:pharmacology; D003599:Cytoskeleton / Q000378:metabolism; D004717:Endometrium / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D005260:Female; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D053583:Interleukin-1beta / Q000494:pharmacology; D008954:Models, Biological; D018994:Myosin Light Chains / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D011247:Pregnancy; D014404:Tubulin / Q000378:metabolism; D014599:Uterus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism
D000199:Actins; D053583:Interleukin-1beta; D018994:Myosin Light Chains; D014404:Tubulin; D000242:Cyclic AMP