维甲酸刺激的肝星状细胞通过转化生长因子-β抑制实质细胞白蛋白的产生。

Retinoic acid-stimulated liver stellate cells suppress the production of albumin from parenchymal cells via TGF-beta.

作者信息

Koda H, Okuno M, Imai S, Moriwaki H, Muto Y, Kawada N, Kojima S

机构信息

First Department of Internal Medicine, Gifu University School of Medicine, Japan.

出版信息

Biochem Biophys Res Commun. 1996 Apr 25;221(3):565-9. doi: 10.1006/bbrc.1996.0636.

DOI:10.1006/bbrc.1996.0636

PMID:8630001

Abstract

We studied a cell-cell interaction via transforming growth factor-beta (TGF-beta ) between liver stellate cells (SCs) and parenchymal cells (PCs) using co-cultures of rat primary SCs and PCs. Both TGF-beta added exogenously to the culture medium, and TGF-beta produced endogenously from SCs after stimulation with retinoic acid (RA), suppressed the production and secretion of albumin from PCs. This effect occurred at the translational level, but not at the transcriptional level; TGF-beta, as well as SC culture medium conditioned by RA, did not affect the albumin mRNA levels, but decreased the biosynthesis of [35-S]methionine-labeled albumin without altering its post-translational degradation rate. These results suggest that TGF-beta generated from SCs facilitates the development of liver cirrhosis not only by inducing the production of fibrotic components from SCs, but also by impairing the function of the surrounding PCs.

摘要

我们使用大鼠原代肝星状细胞（SCs）和实质细胞（PCs）的共培养体系，研究了肝星状细胞与实质细胞之间通过转化生长因子-β（TGF-β）进行的细胞间相互作用。无论是外源添加到培养基中的TGF-β，还是用视黄酸（RA）刺激后肝星状细胞内源性产生的TGF-β，均抑制了实质细胞白蛋白的产生和分泌。这种作用发生在翻译水平，而非转录水平；TGF-β以及经RA处理的肝星状细胞条件培养基，均不影响白蛋白mRNA水平，但降低了[35-S]甲硫氨酸标记的白蛋白的生物合成，且不改变其翻译后降解速率。这些结果表明，肝星状细胞产生的TGF-β不仅通过诱导肝星状细胞产生纤维化成分促进肝硬化的发展，还通过损害周围实质细胞的功能来促进肝硬化发展。