Intercellular communication via gap junctions in activated rat hepatic stellate cells.
OBJECTIVE
Gap junctional communication was studied in quiescent and activated hepatic stellate cells.


METHODS
Connexin expression and intercellular dye transfer were studied in rat hepatic stellate cells in culture and in vivo.


RESULTS
Protein expression of connexin 43 was up-regulated in activated hepatic stellate cells in vivo and in vitro and was mainly localized on the cell surface, whereas connexin 26 was found intracellularly. In contrast to hepatocytes, hepatic stellate cells do not express connexin 32. Confluent hepatic stellate cells in culture communicate via gap junctions, resulting in lucifer yellow transfer and propagation of intracellular calcium signals. Phorbol ester induces a protein kinase C-dependent hyperphosphorylation and degradation of connexin 43 and inhibits intercellular communication on a short-term time scale. At the long-term level, vitamin D(3) , lipopolysaccharide, thyroid hormone T(3), dexamethasone, platelet-derived growth factor, endothelin 1, and interleukin 1beta up-regulate connexin 43 protein and messenger RNA expression and enhance intercellular communication. Slight down-regulation of connexin 43 is observed in response to vitamin A. Connexin 43 induction by endothelin 1 is inhibited by both endothelin A and endothelin B receptor antagonists. In coculture systems, hepatic stellate cells communicate with each other, which is suggestive of a syncytial organization, but no communication was found between hepatic stellate cells and other liver cell types. As shown by immunohistochemistry and electron microscopy, gap junctions are formed between activated hepatic stellate cells in vivo.


CONCLUSIONS
Gap junctional communication occurs between hepatic stellate cells, is enhanced after activation, and underlies complex regulation by cytokines, hormones, and vitamins.
Fischer
Richard
R
Department of Gastroenterology, Hepatology and Infectiology, Heinrich-Heine University, Düsseldorf, Germany.
Reinehr
Roland
R
Lu
Thuy Phung
TP
Schönicke
Alexandra
A
Warskulat
Ulrich
U
Dienes
Hans Peter
HP
Häussinger
Dieter
D
D000818:Animals; D002251:Carbon Tetrachloride; D002252:Carbon Tetrachloride Poisoning / Q000473:pathology; D002450:Cell Communication / Q000502:physiology*; D002478:Cells, Cultured; D018031:Connexin 43 / Q000235:genetics*; D017630:Connexins / Q000235:genetics*; D017629:Gap Junctions / Q000502:physiology*; D005786:Gene Expression Regulation; D008099:Liver / Q000166:cytology / Q000473:pathology / Q000502:physiology*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D000097002:Gap Junction beta-1 Protein
D002251:Carbon Tetrachloride; D018031:Connexin 43; D017630:Connexins; D000097002:Gap Junction beta-1 Protein