Down-regulation of <italic style="font-style: italic">Risa</italic> improves podocyte injury by enhancing autophagy in diabetic nephropathy

Pei-Pei Su; Dong-Wei Liu; Si-Jie Zhou; Hang Chen; Xian-Ming Wu; Zhang-Suo Liu

doi:10.1186/s40779-022-00385-0

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Down-regulation of Risa improves podocyte injury by enhancing autophagy in diabetic nephropathy

RESEARCH | Updated：2023-03-23

- Down-regulation of Risa improves podocyte injury by enhancing autophagy in diabetic nephropathy
- Military Medical Research Vol. 10, Issue 1, Pages: 32-44(2023)
- Affiliations：
  
  1.Department of Nephrology, the First Affiliated Hospital of Zhengzhou University, Research Institutes of Nephropathy, Zhengzhou University, Zhengzhou 450052 , China
  2.Department of Nephrology and Rheumatology, the Third People’s Hospital of Zhengzhou, Zhengzhou 450002 , China
  3.Henan Province Research Center for Kidney Disease, Zhengzhou 450052, China
  4.Key Laboratory of Precision Diagnosis and Treatment for Chronic Kidney Disease in Henan Province, Zhengzhou 450002, China
- Author bio：
  
  * zhangsuoliu@zzu.edu.cn
- Funds：
- DOI：10.1186/s40779-022-00385-0
  CLC：
- Published：2023-02
- Accepted：
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Su PP, Liu DW, Zhou SJ, Chen H, Wu XM, Liu ZS. Down-regulation of Risa improves podocyte injury by enhancing autophagy in diabetic nephropathy. Mil Med Res. 2022;9(1):23.
DOI：

Su PP, Liu DW, Zhou SJ, Chen H, Wu XM, Liu ZS. Down-regulation of Risa improves podocyte injury by enhancing autophagy in diabetic nephropathy. Mil Med Res. 2022;9(1):23. DOI： 10.1186/s40779-022-00385-0.

摘要

Abstract

Background:

LncRNA

AK044604

(regulator of insulin sensitivity and autophagy

Risa

) and autophagy-related factors Sirt1 and GSK3β play important roles in diabetic nephropathy (DN). In this study

we sought to explore the effect of

Risa

on Sirt1/GSK3β-induced podocyte injury.

Methods:

Diabetic db/db mice received

Risa

-inhibition adeno-associated virus (AAV)

via

tail vein injection

and intraperitoneal injection of lithium chloride (LiCl). Blood

urine

and kidney tissue samples were collected and analyzed at different time points. Immortalized mouse podocyte cells (MPCs) were cultured and treated with

Risa

-inhibition lentivirus (LV)

EX-527

and LiCl. MPCs were collected under different stimulations as noted. The effects of

Risa

on podocyte autophagy were examined by qRT-PCR

Western blotting analysis

transmission electron microscopy

Periodic Acid-Schiff staining

and immunofluorescence staining.

Results:

Risa

and activated GSK3β were overexpressed

but Sirt1 was downregulated in DN mice and high glucosetreated MPCs (

0.001

db/m

. db/db

NG or HM

. HG)

which was correlated with poor prognosis.

Risa

overexpression attenuated Sirt1-mediated downstream autophagy levels and aggravated podocyte injury by inhibiting the expression of Sirt1 (

0.001

db/m

. db/db

NG or HM

. HG). In contrast

Risa suppression enhanced Sirt1-induced autophagy and attenuated podocyte injury

which could be abrogated by EX-527 (

0.001

db/db+

Risa

-AAV

. db/db

HG+

Risa

-LV

. HG). Furthermore

LiCl treatment could restore GSK3β-mediated autophagy of podocytes (

0.001

db/db+LiCl

. db/db

HG+LiCl

. HG)

suggesting that

Risa

overexpression aggravated podocyte injury by decreasing autophagy.

Conclusions:

Risa

could inhibit autophagy by regulating the Sirt1/GSK3β axis

thereby aggravating podocyte injury in DN.

Risa

may serve as a therapeutic target for the treatment of DN.

关键词

Keywords

references

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Down-regulation of Risa improves podocyte injury by enhancing autophagy in diabetic nephropathy

DOI：10.1186/s40779-022-00385-0

摘要

Abstract

关键词

Keywords

references