RRC ID 72346
Author Inoue T, Nabeshima K, Shimao Y, Meng JY, Koono M.
Title Regulation of fibronectin expression and splicing in migrating epithelial cells: migrating MDCK cells produce a lesser amount of, but more active, fibronectin.
Journal Biochem Biophys Res Commun
Abstract Previously we have demonstrated that in MDCK epithelial cells not only transforming growth factor-beta (TGF-beta) but also hepatocyte growth factor/scatter factor (HGF/SF) regulates fibronectin (FN) splicing by increasing the ratio of EDA-containing FN (EDA+ FN) mRNA to EDA-minus FN (EDA- FN) mRNA (EDA+/EDA- ratio). EDA+ FN is known to be upregulated in tissues where cells actively migrate, such as those during morphogenesis, wound healing, and tumorigenesis. However, a direct association between cell migration and FN splicing at the EDA region has never been investigated. In this work, we have shown by using an in vitro wound migration assay that migrating epithelial cells regulate FN production and splicing differently compared to nonmigrating cells. Wounds were introduced as migration stimuli into the 10-day-old confluent cell sheet, where the EDA+/EDA- ratio and FN mRNA expression levels were stable. In migrating cells at the wound edge, the FN mRNA level decreased by 0.73-fold and the EDA+/EDA- ratio increased by 1.32-fold when compared with nonmigrating cells apart from the wound edge. HGF/SF significantly stimulated cell migration at the wound edge and concomitantly decreased the FN mRNA level by 0.60-fold and increased the EDA+/EDA- ratio by 1.84-fold in migrating cells. In nonmigrating cells apart from the wound edge, FN mRNA expression and splicing were not influenced by either wound stimulation or HGF/SF. EDA+ FN stimulates cell migration more effectively than EDA- FN and thus is considered to be a more active variant of FN. Taken together, migrating MDCK cells appear to regulate FN mRNA expression and splicing to produce a lesser amount of, but more active, FN.
Volume 280(5)
Pages 1262-8
Published 2001-2-9
DOI 10.1006/bbrc.2001.4264
PII S0006-291X(01)94264-0
PMID 11162664
MeSH Animals Cell Line Cell Movement / physiology* Dogs Epithelial Cells / cytology Epithelial Cells / drug effects Epithelial Cells / metabolism* Fibronectins / genetics* Gene Expression Regulation / drug effects Hepatocyte Growth Factor / pharmacology Humans Kidney / cytology Kidney / drug effects Kidney / metabolism RNA Splicing / drug effects RNA Splicing / genetics* RNA, Messenger / drug effects RNA, Messenger / genetics RNA, Messenger / metabolism Time Factors
IF 2.985
Human and Animal Cells MDCK(RCB0995)