Evidence map›Paper›PMID 34628484›Full record

ArticleCell death & disease2021

AMPK agonist alleviate renal tubulointerstitial fibrosis via activating mitophagy in high fat and streptozotocin induced diabetic mice.

Ya-Chun Han, Shi-Qi Tang, Yu-Ting Liu, Ai-Mei Li, Ming Zhan, Ming Yang, Na Song, Wei Zhang, Xue-Qin Wu, Can-Hui Peng and 2 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell death & disease, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 146 papers.

0numbers the graph read from it
0cells of the map it votes in
146citing papers in PubMed
25.2field-weighted citation impact, top 1% 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

146 citing papers in PubMed, 248 citations in OpenAlex.

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  14. Advances in understanding mitophagy's role in lung injury.Chinese journal of traumatology = Zhonghua chuang shang za zhi · 2026
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86 more citing papers are in PubMed but not listed here.

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 2 institutions in 1 country.

Ya-Chun HanDepartment of Nephrology, The Third Xiangya Hospital, Central South University, Changsha, Hunan, China.
Shi-Qi TangDepartment of Nephrology, The Third Xiangya Hospital, Central South University, Changsha, Hunan, China.
Yu-Ting LiuDepartment of Nephrology, The Third Xiangya Hospital, Central South University, Changsha, Hunan, China.
Ai-Mei LiDepartment of Nephrology, The Third Xiangya Hospital, Central South University, Changsha, Hunan, China.ORCID 0000-0001-7908-9391
Ming ZhanInternational Medicine Department, Ningbo First Hospital, Zhejiang University, Ningbo, China.
Ming YangDepartment of Nephrology, The Second Xiangya Hospital, Institute of Kidney Disease, Central South University, Changsha, Hunan, China.
Na SongDepartment of Nephrology, The Third Xiangya Hospital, Central South University, Changsha, Hunan, China.
Wei ZhangDepartment of Nephrology, The Third Xiangya Hospital, Central South University, Changsha, Hunan, China.ORCID 0000-0001-8679-6713
Xue-Qin WuDepartment of Nephrology, The Third Xiangya Hospital, Central South University, Changsha, Hunan, China.
Can-Hui PengDepartment of Laboratory Medicine, The Third Xiangya Hospital, Central South University, Changsha, China.
Hao ZhangDepartment of Nephrology, The Third Xiangya Hospital, Central South University, Changsha, Hunan, China.
Shikun YangDepartment of Nephrology, The Third Xiangya Hospital, Central South University, Changsha, Hunan, China. ysk_1234@163.com.ORCID 0000-0002-6552-0176
Central South University · CNNingbo First Hospital · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Renal tubulointerstitial fibrosis was a crucial pathological feature of diabetic nephropathy (DN), and renal tubular injury might associate with abnormal mitophagy. In this study, we investigated the effects and molecular mechanisms of AMPK agonist metformin on mitophagy and cellular injury in renal tubular cell under diabetic condition. The high fat diet (HFD) and streptozotocin (STZ)-induced type 2 diabetic mice model and HK-2 cells were used in this study. Metformin was administered in the drinking water (200 mg/kg/d) for 24 weeks. Renal tubulointerstitial lesions, oxidative stress and some indicators of mitophagy (e.g., LC3II, Pink1, and Parkin) were examined both in renal tissue and HK-2 cells. Additionally, compound C (an AMPK inhibitor) and Pink1 siRNA were applied to explore the molecular regulation mechanism of metformin on mitophagy. We found that the expression of p-AMPK, Pink1, Parkin, LC3II, and Atg5 in renal tissue of diabetic mice was decreased obviously. Metformin reduced the levels of serum creatinine, urine protein, and attenuated renal oxidative injury and fibrosis in HFD/STZ induced diabetic mice. In addition, Metformin reversed mitophagy dysfunction and the over-expression of NLRP3. In vitro pretreatment of HK-2 cells with AMPK inhibitor compound C or Pink1 siRNA negated the beneficial effects of metformin. Furthermore, we noted that metformin activated p-AMPK and promoted the translocation of Pink1 from the cytoplasm to mitochondria, then promoted the occurrence of mitophagy in HK-2 cells under HG/HFA ambience. Our results suggested for the first time that AMPK agonist metformin ameliorated renal oxidative stress and tubulointerstitial fibrosis in HFD/STZ-induced diabetic mice via activating mitophagy through a p-AMPK-Pink1-Parkin pathway.

Indexed as

Diet, High-FatMitophagy8-Hydroxy-2'-DeoxyguanosineAMP-Activated Protein KinasesAnimalsBlood GlucoseBlood Urea NitrogenCell LineCollagen Type ICreatinineDiabetes Mellitus, ExperimentalFibronectinsFibrosisHumansInterleukin-1betaKidney8-Hydroxy-2'-DeoxyguanosineAMP-Activated Protein KinasesBlood GlucoseCollagen Type ICreatinineFibronectinsInterleukin-1betaMetforminNLR Family, Pyrin Domain-Containing 3 Proteinparkin proteinProtein KinasesPTEN-Induced Putative KinaseReactive Oxygen SpeciesStreptozocinUbiquitin-Protein Ligases

Identifiers

PMID34628484
PMCPMC8502176
OpenAlexW3212417317

What OpenQuestion holds

Textmetadata
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.