Evidence map›Paper›PMID 35217650›Full record

ArticleCell death & disease2022

Asparaginyl endopeptidase protects against podocyte injury in diabetic nephropathy through cleaving cofilin-1.

Chuntao Lei, Mengran Li, Yang Qiu, Yaru Xie, Zhe Hao, Xingjie Yin, Zhentao Zhang, Hua Su, Linlin Yang, Jihong Lin and 2 more

Open access · goldAbstract read
In one paragraph

Article in Cell death & disease, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed
2.4field-weighted citation impact, top 11% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

14 citing papers in PubMed, 17 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Review
  6. Review
  7. Article
  8. Article
  9. Article
  10. Cytoskeleton Rearrangement in Podocytopathies: An Update.International journal of molecular sciences · 2024
    Review
  11. Article
  12. Article
  13. Article
  14. The Mammalian Cysteine Protease Legumain in Health and Disease.International journal of molecular sciences · 2022
    Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

12 authors at 3 institutions in 2 countries.

Chuntao Lei *Department of Nephrology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
Mengran Li *Department of Nephrology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
Yang QiuDepartment of Nephrology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
Yaru XieDepartment of Nephrology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
Zhe HaoDepartment of Nephrology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
Xingjie YinDepartment of Nephrology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
Zhentao ZhangDepartment of Neurology, Renmin Hospital of Wuhan University, Wuhan, 430060, China.ORCID 0000-0001-6708-1472
Hua SuDepartment of Nephrology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
Linlin Yang5th Medical Department, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
Jihong Lin5th Medical Department, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
Hans-Peter Hammes5th Medical Department, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
Chun ZhangDepartment of Nephrology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China. drzhangchun@hust.edu.cn.ORCID 0000-0003-3565-8024
Union Hospital · CNHeidelberg University · DEWuhan University · CN

Funding

National Natural Science Foundation of China (National Science Foundation of China) 81770711National Natural Science Foundation of China (National Science Foundation of China) 81800610National Natural Science Foundation of China (National Science Foundation of China) 81873602National Natural Science Foundation of China (National Science Foundation of China) 81961138007
6 · The paper itself

Abstract

Podocyte injury and loss are critical events in diabetic nephropathy (DN); however, the underlying molecular mechanisms remain unclear. Here, we demonstrate that asparaginyl endopeptidase (AEP) protects against podocyte injury through modulating the dynamics of the cytoskeleton. AEP was highly upregulated in diabetic glomeruli and hyperglycemic stimuli treated-podocytes; however, AEP gene knockout and its compound inhibitor treatment accelerated DN in streptozotocin-induced diabetic mice, whereas specific induction of AEP in glomerular cells attenuated podocyte injury and renal function deterioration. In vitro, elevated AEP was involved in actin cytoskeleton maintenance and anti-apoptosis effects. Mechanistically, we found that AEP directly cleaved the actin-binding protein cofilin-1 after the asparagine 138 (N138) site. The protein levels of endogenous cofilin-1 1-138 fragments were upregulated in diabetic podocytes, consistent with the changes in AEP levels. Importantly, we found that cofilin-1 1-138 fragments were remarkably unphosphorylated than full-length cofilin-1, indicating the enhanced cytoskeleton maintenance activity of cofilin-1 1-138. Then we validated cofilin-1 1-138 could rescue podocytes from cytoskeleton disarrangement and injury in diabetic conditions. Taken together, our data suggest a protective role of elevated AEP in podocyte injury during DN progression through cleaving cofilin-1 to maintain podocyte cytoskeleton dynamics and defend damage.

Indexed as

Diabetes Mellitus, ExperimentalDiabetic NephropathiesPodocytesActin Depolymerizing FactorsAnimalsAsparaginyl EndopeptidaseCysteine EndopeptidasesMiceMice, Inbred C57BLActin Depolymerizing FactorsAsparaginyl EndopeptidaseCysteine Endopeptidases

Identifiers

PMID35217650
PMCPMC8881581
OpenAlexW4214511500

What OpenQuestion holds

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LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.