Retinoic acid enhances connexin43 expression at the post‐transcriptional level in rat liver epithelial cells

Abstract

The mechanism by which all-trans retinoic acid (RA) stimulates gap junctional intercellular communication (GJIC) in the rat liver epithelial cell line. IAR203, was investigated. When RA, at 0.1 microM for 24-48 h, enhanced the dye transfer in IAR203 cells (x 1.4), it increased the amount of connexin43 (Cx43) in the cell-cell contact regions of the plasma membrane, as evidenced by analysis by Western blot and by immunofluorescence. It had no effect on the level of Cx43 mRNA. Freeze-fracture analysis of the size of gap junctions revealed an increase of the proportion of small gap junctions in RA-treated cells. We conclude that, in IAR203 cells, RA stimulates GJIC by acting at the post-transcriptional level of Cx43 regulation. The possibility that RA acts indirectly on the regulation of Cx43 expression, and increases the half-life of Cx43 by inducing adhesion molecules is discussed.

Direct gating by retinoic acid of retinal electrical synapses

“…Although previous reports have shown that RA can modulate dye coupling by regulating connexin expression at the transcription level in other tissues (19)(20)(21)(22)(23), our results indicate that RA potently and directly gates electrical coupling in retinal neurons.…”

“…First, the time course of RA action on horizontal cell coupling is much more rapid than the previously reported transcriptional effects of RA on cell coupling. RA is known to up-regulate or down-regulate connexin gene expression via RAR͞RXR activation in the nucleus, resulting in a change in dye coupling between RAtreated cells in several cell lines (19)(20)(21)(22)(23). However, these nonreversible changes take place over the course of hours or days.…”

Analysis of connexin43 gene expression induced by retinoic acid in F9 teratocarcinoma cells

“…Our results differ in part from those by Bex et al [14] obtained with the rat liver epithelial cell line IAR 203 cells. These authors treated IAR 203 cells with retinoic acid in concentrations of 10 -7 M for 48 h and observed an increase of intercellular communication, an increase in the amount of the gap junction protein connexin43, but no increase in the level of connexin43 mRNA.…”

“…This process is accompanied by changes in cell morphology and in the expression of several genes, for example col lagen IV and laminin [4,8] and in differentiated F9 cells, whereas mRNA of connexin32 is not detectable in stem cells [9]. In other cell systems, we and others have shown that treatment of the cells with retinoic acid in physiological concentrations leads to an increase of intercellular communication [10][11][12][13][14] associated with an increased amount of connexin43 mRNA [10][11][12][13] or connexin43 protein [14].…”

Inhibition of cellular proliferation and modulation of insulin-like growth factor binding proteins by retinoids in a bovine mammary epithelial cell line

“…On the other hand, maximal growth inhibition of RA occurs at cytotoxic levels. These concentrations of RA and retino1 exert physiological noncytotoxic effects in other cell lines (Moore et al, 1992;Bex et al, 1995). Finally and perhaps the most dramatic difference between TGF-Pand RA-induced growth inhibition of MAC-T cells is TGF-P has no demonstrable effect on IGFBP profiles in the presence or absence of insulidGF-I.…”