Adenine Induces Differentiation of Rat Hepatic Stellate Cells

作者：Watanabe Azuma; Sohail Muhammad Adnan; Gautam Samir; Gomes Dawidson Assis; Mehal Wajahat Zafar^*

来源：Digestive Diseases and Sciences, 2012, 57(9): 2371-2378.

DOI：10.1007/s10620-012-2183-7

• Adenine
• Stellate cells
• Chemotaxis
• Differentiation

Adenine is a uric acid pathway metabolite of no known function, and has recently been identified as a ligand for a rat G protein-coupled receptor. Due to the known role of other uric acid pathway metabolites in HSC biology, we tested the ability of adenine to induce HSC differentiation. %26lt;br%26gt;RT-PCR was performed for adenine receptor expression in T-6 and primary rat HSC. T-6 and primary rats HSC were cultured with and without adenine, and stellation examined. Next, we examined inhibition of calcium signaling using caged IP3. To test if adenine inhibits HSC chemotaxis T-6 cells and rat HSCs were cultured with or without adenine for 24 h in a transwell assay with PDGF as the chemoattractant. cDNA was prepared from T-6 and primary HSC for quantification of collagen 1 mRNA using real-time PCR. %26lt;br%26gt;We found that mRNA for the adenine receptor is expressed in T-6 cells and primary rat HSC. Also, adenine induces HSC stellation and adenine inhibits IP3 mediated increase in cytosolic [Ca2+](i) and inhibits chemotaxis in T-6 cells and primary rat HSC. Adenine was also shown to up-regulate alpha-SMA and collagen 1, and this effect is lost by using specific si-RNA for the adenine receptor. Finally, adenine inhibits endothelin-1-induced gel contraction. %26lt;br%26gt;The adenine receptor is present in T-6 cells and primary rats HSC. Adenine, via the adenine receptor, induces morphological change, and cytosolic calcium signaling, inhibits chemotaxis, and up-regulates collagen 1 mRNA in HSCs.

• 出版日期2012-9