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Human hepatic stellate cells secrete adrenomedullin: potential autocrine factor in the regulation of cell contractility.

Abstract：

BACKGROUND/AIMS:Hepatic stellate cells (HSCs) are perisinusoidal pericytes which have receptors for vasoactive factors, such as endothelin-1, which can regulate cell contractility in an autocrine manner. It is unknown whether human HSCs have receptors for and are able to synthesize the vasodilator peptide adrenomedullin (ADM), a peptide produced by most contractile cells. METHODS AND RESULTS:Stimulation of HSCs with ADM resulted in a dose-dependent raise in cAMP concentration (radioimmunoassay) and markedly blunted the endothelin-induced increase in [Ca2+]i and cell contraction, as assessed in cells loaded with fura-2 using a morphometric method. The existence of the receptor CRLR for ADM and their associated proteins RAMP-1 and RAMP-2 was demonstrated by reverse transcriptase-polymerase chain reaction (RT-PCR). Moreover, activated human HSCs spontaneously secreted ADM in the culture medium in a time-dependent manner. ADM secretion was markedly enhanced by tumour necrosis factor-alpha and interleukin-1beta. Specific mRNA for ADM (RT-PCR and Northern blot) was detected in HSCs and increased after incubation of cells with cytokines. CONCLUSIONS:Human HSCs have functional receptors for ADM, the stimulation of which blunts the contractile effect of endothelin-1. Cultured human HSCs secrete ADM in baseline conditions. This secretion is markedly increased by cytokines. These results suggest that ADM can regulate HSCs' contractility in an autocrine manner.

journal_name

J Hepatol

journal_title

Journal of hepatology

authors

Görbig MN,Ginès P,Bataller R,Nicolás JM,Garcia-Ramallo E,Cejudo P,Sancho-Bru P,Jiménez W,Arroyo V,Rodés J

doi

10.1016/s0168-8278(00)00016-7

subject

Has Abstract

pub_date

2001-02-01 00:00:00

pages

222-9

issue

2

eissn

0168-8278

issn

1600-0641

pii

S0168827800000167

journal_volume

34

pub_type

杂志文章

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