Abstract
Metastasis associated lung adenocarcinoma transcript 1(MALAT1) is a long non-coding RNA, broadly expressed in mammalian tissues including kidney and up-regulated in a variety of cancer cells. To date, its functions in podocytes are largely unknown. β-catenin is a key mediator in the canonical and non-canonical Wnt signalling pathway; its aberrant expression promotes podocyte malfunction and albuminuria, and contributes to kidney fibrosis. In this study, we found that MALAT1 levels were increased in kidney cortices from C57BL/6 mice with streptozocin (STZ)-induced diabetic nephropathy, and dynamically regulated in cultured mouse podocytes stimulated with high glucose, which showed a trend from rise to decline. The decline of MALAT1 levels was accompanied with β-catenin translocation to the nuclei and enhanced expression of serine/arginine splicing factor 1 (SRSF1), a MALAT1 RNA-binding protein. Further we showed early interference with MALAT1 siRNA partially restored podocytes function and prohibited β-catenin nuclear accumulation and SRSF1 overexpression. Intriguingly, we showed that β-catenin was involved in MALAT1 transcription by binding to the promotor region of MALAT1; β-catenin knock-down also decreased MALAT1 levels, suggesting a novel feedback regulation between MALAT1 and β-catenin. Notably, β-catenin deletion had limited effects on SRSF1 expression, demonstrating β-catenin might serve as a downstream signal of SRSF1. These findings provided evidence for a pivotal role of MALAT1 in diabetic nephropathy and high glucose-induced podocyte damage.