PMID- 11162664 OWN - NLM STAT- MEDLINE DCOM- 20010315 LR - 20041117 IS - 0006-291X (Print) IS - 0006-291X (Linking) VI - 280 IP - 5 DP - 2001 Feb 9 TI - Regulation of fibronectin expression and splicing in migrating epithelial cells: migrating MDCK cells produce a lesser amount of, but more active, fibronectin. PG - 1262-8 AB - 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. FAU - Inoue, T AU - Inoue T AD - Department of Pathology, Miyazaki Medical College, 5200 Kihara, Kiyotake, Miyazaki, 889-1692, Japan. FAU - Nabeshima, K AU - Nabeshima K FAU - Shimao, Y AU - Shimao Y FAU - Meng, J Y AU - Meng JY FAU - Koono, M AU - Koono M LA - eng PT - Journal Article PL - United States TA - Biochem Biophys Res Commun JT - Biochemical and biophysical research communications JID - 0372516 RN - 0 (Fibronectins) RN - 0 (RNA, Messenger) RN - 67256-21-7 (Hepatocyte Growth Factor) SB - IM MH - Animals MH - Cell Line MH - Cell Movement/*physiology MH - Dogs MH - Epithelial Cells/cytology/drug effects/*metabolism MH - Fibronectins/*genetics MH - Gene Expression Regulation/drug effects MH - Hepatocyte Growth Factor/pharmacology MH - Humans MH - Kidney/cytology/drug effects/metabolism MH - RNA Splicing/drug effects/*genetics MH - RNA, Messenger/drug effects/genetics/metabolism MH - Time Factors EDAT- 2001/02/13 11:00 MHDA- 2001/03/17 10:01 CRDT- 2001/02/13 11:00 PHST- 2001/02/13 11:00 [pubmed] PHST- 2001/03/17 10:01 [medline] PHST- 2001/02/13 11:00 [entrez] AID - S0006-291X(01)94264-0 [pii] AID - 10.1006/bbrc.2001.4264 [doi] PST - ppublish SO - Biochem Biophys Res Commun. 2001 Feb 9;280(5):1262-8. doi: 10.1006/bbrc.2001.4264.