BMP-9 Modulates the Hepatic Responses to LPS.

Cells
Haristi GaitantziKatja Breitkopf-Heinlein

Abstract

It was previously shown that Bone Morphogenetic Protein (BMP)-9 is constitutively produced and secreted by hepatic stellate cells (HSC). Upon acute liver damage, BMP-9 expression is transiently down-regulated and blocking BMP-9 under conditions of chronic damage ameliorated liver fibrogenesis in C57BL/6 mice. Thereby, BMP-9 acted as a pro-fibrogenic cytokine in the liver but without directly activating isolated HSC in vitro. Lipopolysaccharide (LPS), an endotoxin derived from the membrane of Gram-negative bacteria in the gut, is known to be essential in the pathogenesis of diverse kinds of liver diseases. The aim of the present project was therefore to investigate how high levels of BMP-9 in the context of LPS signalling might result in enhanced liver damage. For this purpose, we stimulated human liver sinusoidal endothelial cells (LSEC) with LPS and incubated primary human liver myofibroblasts (MF) with the conditioned medium of these cells. We found that LPS led to the secretion of factors from LSEC that upregulate BMP-9 expression in MF. At least one of these BMP-9 enhancing factors was defined to be IL-6. High BMP-9 in turn, especially in combination with LPS stimulation, induced the expression of certain capillarization ma...Continue Reading

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Citations

Oct 31, 2020·Cells·Isabel FabregatAránzazu Sánchez
Mar 18, 2021·Molecular Biology Reports·Heming MaJunqi Niu
May 22, 2021·Molecular and Cellular Biochemistry·Qian-Qian JiangKe-Shu Xu
Jul 7, 2021·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Eréndira Guadalupe Pérez-HernándezJaime Mas-Oliva

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Methods Mentioned

BETA
PCR
FCS
chip
protein
Protein Assay
ELISA

Software Mentioned

- Win64
limma
GraphPad Prism
Affymetrix
ImageJ

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