Regulation of fibronectin alternative splicing by a basement membrane-like extracellular matrix.
Hepatocytes are the source of plasma fibronectin (FN) which lacks the alternatively spliced EDI segment, distinctive of oncofetal FN. When hepatic or other epithelial cells are cultured on plastic, EDI inclusion is triggered. Here we report that EDI inclusion is inhibited when hepatic cells are cultured on a basement membrane-like extracellular matrix (ECM), demonstrating a new role for the ECM in the control of gene expression. The effect is duplicated by collagen IV and laminin but not by collagen I; is not observed with another alternatively spliced FN exon (EDII); and correlates with a decrease in cell proliferation, consistently with high EDI inclusion levels observed in many physiological and pathological proliferative processes.
Srebrow
Anabella
A
Departamento de Fisiología, Biología Molecular y Celular, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Ciudad Universitaria, Pabellón II (C1428EHA), Buenos Aires, Argentina. asrebrow@bg.fcen.uba.ar
Blaustein
Matías
M
Kornblihtt
Alberto R
AR
D017398:Alternative Splicing / Q000187:drug effects / Q000502:physiology*; D001485:Basement Membrane / Q000378:metabolism*; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D003094:Collagen / Q000494:pharmacology; D024042:Collagen Type I / Q000494:pharmacology; D024141:Collagen Type IV / Q000494:pharmacology; D004338:Drug Combinations; D005091:Exons; D005109:Extracellular Matrix / Q000502:physiology*; D005353:Fibronectins / Q000235:genetics*; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D022781:Hepatocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D007797:Laminin / Q000494:pharmacology; D011509:Proteoglycans / Q000494:pharmacology; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D014162:Transfection
D024042:Collagen Type I; D024141:Collagen Type IV; D004338:Drug Combinations; D005353:Fibronectins; D007797:Laminin; D011509:Proteoglycans; D012333:RNA, Messenger; C059485:matrigel; D003094:Collagen