Background: Tubular injury is considered as a crucial pathological feature of diabetic nephropathy. LncRNA MALAT1 is involved in diabetic complications. Hence the role of MALAT1 in high glucose induced renal tubular epithelial cells (HK-2) injury deserves investigation. Methods: The diabetic mice model was established with streptozotocin (STZ) injection. The expression of NEAT1, SIRT1, and Foxo1 mRNA and protein was determined with qRT-PCR and western blot, respectively. The serum creatinine and urinary albumin were examined by enzyme linked immunosorbent assay (ELISA). Interaction between MALAT1 and Foxol was detected with RIP and RNA pull-down assay, respectively. Dual luciferase reporter assay was used to evaluate the binding between Foxol and SIRT1. Results: LncRNA MALAT1 was up-regulated in kidney tissues of diabetic mice and in HK-2 cells treated with high glucose, while the expression of SIRT1 was decreased. Interaction between MALAT1 and Foxol was observed in HK-2 cells and the interaction was promoted by high glucose treatment. Foxol activated SIRT1 transcription by binding to its promoter, and MALAT1 repressed SIRT1 expression through targeting Foxol. Conclusion: LncRNA MALAT1 interacts with transcription factor Foxol to represses SIRT1 transcription in high glucose incubated HK-2 cells, which promotes high glucose-induced HK-2 cells injury. (C) 2018 Elsevier Inc. All rights reserved.