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BMP-2 restoration aids in recovery from liver fibrosis by attenuating TGF-β1 signaling
Transforming growth factor-β (TGF-β) plays a central role in hepatic fibrogenesis. This study investigated the function and mechanism of bone morphogenetic protein-2 (BMP-2) in regulation of hepatic fibrogenesis. BMP-2 expression in fibrotic liver was measured in human tissue microarray and mouse models of liver fibrosis induced by bile duct ligation surgery or carbon tetrachloride administration. Adenovirus-mediated BMP-2 gene delivery was used to test the prophylactic effect on liver fibrosis. Primary hepatic stellate cells (HSC), HSC-T6 and clone-9 cell lines were used to study the interplay between BMP-2 and TGF-β1. Hepatic BMP-2 was localized in parenchymal hepatocytes and activated HSCs and significantly decreased in human and mouse fibrotic livers, showing an opposite pattern of hepatic TGF-β1 contents. BMP-2 gene delivery alleviated the elevations of serum hepatic enzymes, cholangiocyte marker CK19, HSC activation markers, and liver fibrosis in both models. Mechanistically, exogenous TGF-β1 dose dependently reduced BMP-2 expression, whereas BMP-2 significantly suppressed expression of TGF-β and its cognate type I and II receptor peptides, as well as the induced Smad3 phosphorylation levels in primary mouse HSCs. Aside from its suppressive effects on cell proliferation and migration, BMP-2 treatment prominently attenuated the TGF-β1-stimulated α-SMA and fibronectin expression, and reversed the TGF-β1-modulated epithelial-to-mesenchymal transition marker expression in mouse HSCs. The mutual regulation between BMP-2 and TGF-β1 signaling axes may constitute the anti-fibrogenic mechanism of BMP-2 in the pathogenesis of liver fibrosis. BMP-2 may potentially serve as a novel therapeutic target for treatment of liver fibrosis.
Response to 'Evolving M-protein pattern in patients with smoldering multiple myeloma: impact on early progression'
Response to 'Evolving M-protein pattern in patients with smoldering multiple myeloma: impact on early progression', Published online: 25 May 2018; doi:10.1038/s41375-018-0155- ... mehr
Coppery inks paint an underwater rainbow
Coppery inks paint an underwater rainbow, Published online: 25 May 2018; doi:10.1038/d41586-018-05282-y
Inexpensive version of luminescent pigment shrugs off water. mehr
Previous studies suggested that MeCP2 competes with linker histone H1, but this hypothesis has never been tested in vivo. Here, we performed chromatin immunoprecipitation followed by sequencing (ChIP-seq) of Flag-tagged-H1.0 in mouse forebrain excitatory neurons. Unexpectedly, Flag-H1.0 and ... mehr
(dpa) Zwei Expertinnen aus Deutschland gehören für das britische Fachmagazin «Nature» zu den zehn Menschen, die im Jahr 2020 eine entscheidende Rolle für die Wissenschaft spielten: die gebürtige Erfurterin Kathrin Jansen, Leiterin der Impfstoff-Forschung beim US-Pharmaunternehmen Pfizer, so ... mehr
(dpa) Vom visionären Quanten-Physiker über den Experten für Gen-Editing bis hin zum umstrittenen neuen Chef der US-Umweltbehörde EPA - sie alle gehören zu den zehn Menschen, die nach Ansicht des Fachmagazins «Nature» im Jahr 2017 eine entscheidende Rolle in der Wissenschaft gespielt haben. ... mehr
(dpa) Die laut «Nature» einflussreichsten Forscher des Jahres 2016 haben ein breites Themenspektrum. Ihre Arbeitsgebiete reichen von Gravitationswellen über Künstliche Intelligenz bis hin zu den Rechten von Minderheiten in der Wissenschaft. «Die Wissenschaftler auf der 2016 Nature-Zehnerlis ... mehr