Abstract: Objective To explore the effects and mechanisms of RNA interference mediated by lentivirus down-regulating acetyl CoA carboxylase 2 (ACC2) on intracellular lipid accumulation and epithelial mesenchymal transition (EMT) in high glucose cultured human renal proximal tubular epithelial cells (HKC). Methods The lentivirus vector based on small hairpin RNA (shRNA) targeting ACC2 was constructed and delivered to HKC cells cultured in high glucose. Then the cells were divided into 5 groups: normal glucose group (5.5 mmol/L glucose, NG group), high glucose group (30 mmol/L glucose, HG group), high osmotic pressure control group (5.5mmol/L glucose plus 24.5 mmol/L mannitol, HO group), ACC2-shRNA group (30 mmol/L glucose plus ACC2-shRNA lentivirous), and NC-shRNA group (30 mmol/L glucose plus empty lentivirous carrying the green fluorescent protein as negative control). After treated for 96 h, morphology change of HKC cells was observed under microscope, intracellular lipid accumulation was obtained by Oil Red O staining, and E-cadherin and α-SMA protein levels were detected by Western blotting. Results High glucose induced morphology change and intracellular lipid accumulation of cultured HKC cells. Protein level of E-cadherin was decreased, while α-SMA was increased(P<0.05). Interference of ACC2 successfully restored high glucose stimulated morphology change and cellular lipid accumulation; the expression level of E-cadherin protein was increased and α-SMA protein was reduced. Conclusion Interference of ACC2 can ameliorate high glucosestimulated cellular lipid accumulation and epithelial mesenchymal transition, then improve renal fibrosis.

Key words: Acetyl CoA carboxylase 2, Diabetic nephropathy, RNA interference, Lipotoxicity, Epithelial mesenchymal transition