Connexin expression by alveolar epithelial cells is regulated by extracellular matrix.
Extracellular matrix (ECM) proteins promote attachment, spreading, and differentiation of cultured alveolar type II epithelial cells. The present studies address the hypothesis that the ECM also regulates expression and function of gap junction proteins, connexins, in this cell population. Expression of cellular fibronectin and connexin (Cx) 43 increase in parallel during early type II cell culture as Cx26 expression declines. Gap junction intercellular communication is established over the same interval. Cells plated on a preformed, type II cell-derived, fibronectin-rich ECM demonstrate accelerated formation of gap junction plaques and elevated gap junction intercellular communication. These effects are blocked by antibodies against fibronectin, which cause redistribution of Cx43 protein from the plasma membrane to the cytoplasm. Conversely, cells cultured on a laminin-rich ECM, Matrigel, express low levels of Cx43 but high levels of Cx26, reflecting both transcriptional and translational regulation. Cx26 and Cx43 thus demonstrate reciprocal regulation by ECM constituents.
Guo
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Y
Department of Cellular and Molecular Physiology, The Pennsylvania State University College of Medicine, Hershey, Pennsylvania 17033, USA.
Martinez-Williams
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C
Yellowley
C E
CE
Donahue
H J
HJ
Rannels
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DE
D000818:Animals; D019138:Antibodies, Blocking / Q000494:pharmacology; D002450:Cell Communication / Q000187:drug effects / Q000502:physiology; D002462:Cell Membrane / Q000378:metabolism; D002478:Cells, Cultured; D000072259:Connexin 26; D018031:Connexin 43 / Q000096:biosynthesis; D017630:Connexins / Q000096:biosynthesis* / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D005109:Extracellular Matrix / Q000378:metabolism*; D016326:Extracellular Matrix Proteins / Q000378:metabolism / Q000494:pharmacology; D005353:Fibronectins / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D005456:Fluorescent Dyes; D017629:Gap Junctions / Q000378:metabolism; D007150:Immunohistochemistry; D007546:Isoquinolines; D007797:Laminin / Q000378:metabolism; D008297:Male; D011650:Pulmonary Alveoli / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
D019138:Antibodies, Blocking; D018031:Connexin 43; D017630:Connexins; C411002:ECM3 protein, Lytechinus variegatus; D016326:Extracellular Matrix Proteins; D005353:Fibronectins; D005456:Fluorescent Dyes; C000607044:Gjb2 protein, rat; D007546:Isoquinolines; D007797:Laminin; D000072259:Connexin 26; C017475:lucifer yellow