Changes in microRNAs associated with hepatic stellate cell activation status identify signaling pathways.
Activation of hepatic stellate cells (HSCs), which is regulated by multiple signal transduction pathways, is the key event in liver fibrosis. Moreover, members of these pathways are important targets for microRNAs (miRNAs). To better understand the critical pathways of HSC activation, we performed comprehensive comparative bioinformatics analysis of microarrays of quiescent and activated HSCs. Changes in miRNAs associated with HSC activation status revealed that 13 pathways were upregulated and 22 pathways were downregulated by miRNA. Furthermore, mitochondrial integrity, based on highly upregulated Bcl-2 and downregulated caspase-9, was confirmed in HSCs and fibrotic livers by immnofluorescence assay, quantitative RT-PCR, and western blot analysis. These findings provide in vitro and in vivo evidence that the mitochondrial pathway of apoptosis plays a significant role in the progression of liver fibrogenesis via HSC activation.
Guo
Can-Jie
CJ
Digestive Disease Laboratory and Department of Gastroenterology, Xinhua Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China.
Pan
Qin
Q
Cheng
Tao
T
Jiang
Bo
B
Chen
Guang-Yu
GY
Li
Ding-Guo
DG
D000818:Animals; D017209:Apoptosis; D002251:Carbon Tetrachloride / Q000633:toxicity; D019295:Computational Biology; D055166:Hepatic Stellate Cells / Q000502:physiology*; D008106:Liver Cirrhosis, Experimental / Q000139:chemically induced; D035683:MicroRNAs / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000502:physiology*
D035683:MicroRNAs; D002251:Carbon Tetrachloride