I recently analyzed RT PCR data for NASH livers. Oil red O staining revealed that my experimental group has exacerbated NASH/ lipid content. This group also demonstrates lower RNA expression of Srebp2, Hmgcr, and Hmgcs. However the gene expression of Ldlr is drastically increased. These results should be validated with western blot analysis also but does anyone know why this might be? PCSK9 is a post transcriptional inhibitor of Ldlr, so this wouldn't affect Ldlr on a transcriptional level.
Hi Joselyn
While cellular sterol-mediated transcription of LDL receptor gene is a well known mechanism to regulate ldlr gene expression, it is not the only regulatory component of ldlr transcription. The induction of ldlr gene can also occur if the hepatocyte growth factor (HGF) is higher. HGF acts as a mitogenic stimulus for regeneration of liver, and may override sterol-mediated repression of LDL receptor gene transcription. This is independent to SREBP2 pathway. In NASH livers, studies have shown higher levels of HGF which might be a reason for an increased ldlr mRNA expression in your study.
Check out these papers:
http://www.jlr.org/content/37/5/985.full.pdf
https://www.ncbi.nlm.nih.gov/pubmed/16807517
Best,
Shruti
- Badges
- Science topic
- Similar topics
- Mathematics
- Statistics
- Sampling Design
- Sample Size