LncRNA MALAT1 is dysregulated in diabetic nephropathy and involved in high glucose‐induced podocyte injury via its interplay with β‐catenin

摘要

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 style="fixed-case">SRSF1 expression, demonstrating β‐catenin might serve as a downstream signal of style="fixed-case">SRSF1. These findings provided evidence for a pivotal role of style="fixed-case">MALAT1 in diabetic nephropathy and high glucose‐induced podocyte damage.