Connexin expression by alveolar epithelial cells is regulated by extracellular matrix

Extracellular matrix (ECM) proteins promote attachment, spreading, and diff erentiation of cultured alveolar type II epithelial cells. The present stud ies address the hypothesis that the ECM also regulates expression and funct ion of gap junction proteins, connexins, in this cell population. Expressio n of cellular fibronectin and connexin (Cx) 43 increase in parallel during early type II cell culture as Cx26 expression declines. Gap junction interc ellular communication is established over the same interval. Cells plated o n a preformed, type II cell-derived, fibronectin-rich ECM demonstrate accel erated formation of gap junction plaques and elevated gap junction intercel lular communication. These effects are blocked by antibodies against fibron ectin, which cause redistribution of Cx43 protein from the plasma membrane to the cytoplasm. Conversely, cells cultured on a laminin-rich ECM, Matrige l, express low levels of Cx43 but high levels of Cx26, reflecting both tran scriptional and translational regulation. Cx26 and Cx43 thus demonstrate re ciprocal regulation by ECM constituents.