Unknown

Dataset Information

0

Transcriptome-based repurposing of apigenin as a potential anti-fibrotic agent targeting hepatic stellate cells.


ABSTRACT: We have used a computational approach to identify anti-fibrotic therapies by querying a transcriptome. A transcriptome signature of activated hepatic stellate cells (HSCs), the primary collagen-secreting cell in liver, and queried against a transcriptomic database that quantifies changes in gene expression in response to 1,309 FDA-approved drugs and bioactives (CMap). The flavonoid apigenin was among 9 top-ranked compounds predicted to have anti-fibrotic activity; indeed, apigenin dose-dependently reduced collagen I in the human HSC line, TWNT-4. To identify proteins mediating apigenin's effect, we next overlapped a 122-gene signature unique to HSCs with a list of 160 genes encoding proteins that are known to interact with apigenin, which identified C1QTNF2, encoding for Complement C1q tumor necrosis factor-related protein 2, a secreted adipocytokine with metabolic effects in liver. To validate its disease relevance, C1QTNF2 expression is reduced during hepatic stellate cell activation in culture and in a mouse model of alcoholic liver injury in vivo, and its expression correlates with better clinical outcomes in patients with hepatitis C cirrhosis (n?=?216), suggesting it may have a protective role in cirrhosis progression.These findings reinforce the value of computational approaches to drug discovery for hepatic fibrosis, and identify C1QTNF2 as a potential mediator of apigenin's anti-fibrotic activity.

SUBMITTER: Hicks DF 

PROVIDER: S-EPMC5335661 | biostudies-literature | 2017 Mar

REPOSITORIES: biostudies-literature

altmetric image

Publications


We have used a computational approach to identify anti-fibrotic therapies by querying a transcriptome. A transcriptome signature of activated hepatic stellate cells (HSCs), the primary collagen-secreting cell in liver, and queried against a transcriptomic database that quantifies changes in gene expression in response to 1,309 FDA-approved drugs and bioactives (CMap). The flavonoid apigenin was among 9 top-ranked compounds predicted to have anti-fibrotic activity; indeed, apigenin dose-dependent  ...[more]

Similar Datasets

| S-EPMC6402399 | biostudies-literature
| S-EPMC8705910 | biostudies-literature
| S-EPMC3370152 | biostudies-literature
| S-EPMC7370813 | biostudies-literature
| S-EPMC8654208 | biostudies-literature
2024-10-17 | PXD052809 | Pride
| S-EPMC4253440 | biostudies-literature
| S-EPMC6102213 | biostudies-literature
| S-EPMC5473841 | biostudies-literature
| S-EPMC5156597 | biostudies-literature