In:
Journal of Cellular and Molecular Medicine, Wiley, Vol. 21, No. 11 ( 2017-11), p. 2732-2747
Abstract:
Metastasis associated lung adenocarcinoma transcript 1( MALAT 1) 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 MALAT 1 levels were increased in kidney cortices from C57 BL /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 MALAT 1 levels was accompanied with β‐catenin translocation to the nuclei and enhanced expression of serine/arginine splicing factor 1 ( SRSF 1), a MALAT 1 RNA ‐binding protein. Further we showed early interference with MALAT 1 si RNA partially restored podocytes function and prohibited β‐catenin nuclear accumulation and SRSF 1 overexpression. Intriguingly, we showed that β‐catenin was involved in MALAT 1 transcription by binding to the promotor region of MALAT 1; β‐catenin knock‐down also decreased MALAT 1 levels, suggesting a novel feedback regulation between MALAT 1 and β‐catenin. Notably, β‐catenin deletion had limited effects on SRSF 1 expression, demonstrating β‐catenin might serve as a downstream signal of SRSF 1. These findings provided evidence for a pivotal role of MALAT 1 in diabetic nephropathy and high glucose‐induced podocyte damage.
Type of Medium:
Online Resource
ISSN:
1582-1838
,
1582-4934
DOI:
10.1111/jcmm.2017.21.issue-11
Language:
English
Publisher:
Wiley
Publication Date:
2017
detail.hit.zdb_id:
2076114-4
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