Evidence map›Paper›PMID 25885904›Full record

ArticleBMC cell biology2015

AKT regulation of mesothelial-to-mesenchymal transition in peritoneal dialysis is modulated by Smurf2 and deubiquitinating enzyme USP4.

Li Xiao, Xiang Peng, Fuyou Liu, Chengyuan Tang, Chun Hu, Xiaoxuan Xu, Ming Wang, Ying Luo, Shikun Yang, Panai Song and 3 more

Open access · goldAbstract read
In one paragraph

Article in BMC cell biology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.

0numbers the graph read from it
0cells of the map it votes in
17citing papers in PubMed
2.5field-weighted citation impact, top 12% 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

17 citing papers in PubMed, 31 citations in OpenAlex.

  1. Article
  2. Expression and Role of Ubiquitin-Specific Peptidases in Osteoblasts.International journal of molecular sciences · 2021
    Review
  3. Article
  4. Article
  5. Spotlight on USP4: Structure, Function, and Regulation.Frontiers in cell and developmental biology · 2021
    Review
  6. Review
  7. Article
  8. Article
  9. Article
  10. Article
  11. Article
  12. Review
  13. Deubiquitinating Enzymes and Bone Remodeling.Stem cells international · 2018
    Review
  14. Article
  15. Article
  16. Article
  17. Article
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

13 authors at 3 institutions in 2 countries.

Li XiaoDepartment of Nephrology, Second Xiangya Hospital, Central South University, Changsha, Hunan, 410011, China. xiaolidoc@aliyun.com.
Xiang PengDepartment of Nephrology, Second Xiangya Hospital, Central South University, Changsha, Hunan, 410011, China. pengxiangxy@163.com.
Fuyou LiuDepartment of Nephrology, Second Xiangya Hospital, Central South University, Changsha, Hunan, 410011, China. liufuyoukidney@163.com.
Chengyuan TangDepartment of Nephrology, Second Xiangya Hospital, Central South University, Changsha, Hunan, 410011, China. Tangcy12@163.com.
Chun HuDepartment of Nephrology, Second Xiangya Hospital, Central South University, Changsha, Hunan, 410011, China. huchunly@126.com.
Xiaoxuan XuDepartment of Nephrology, Second Xiangya Hospital, Central South University, Changsha, Hunan, 410011, China. xu129214@163.com.
Ming WangDepartment of Nephrology, Second Xiangya Hospital, Central South University, Changsha, Hunan, 410011, China. wangminggoodlk@163.com.
Ying LuoDepartment of Nephrology, Second Xiangya Hospital, Central South University, Changsha, Hunan, 410011, China. luoying2420@163.com.
Shikun YangDepartment of Nephrology, Second Xiangya Hospital, Central South University, Changsha, Hunan, 410011, China. ysk_1234@163.com.
Panai SongDepartment of Nephrology, Second Xiangya Hospital, Central South University, Changsha, Hunan, 410011, China. spa863@163.com.
Ping XiaoDepartment of Nephrology, Second Xiangya Hospital, Central South University, Changsha, Hunan, 410011, China. xiaopingxy3366@163.com.
Yashpal S KanwarDepartments of Pathology & Medicine, Northwestern University, Chicago, USA. y-kanwar@northwestern.edu.
Lin SunDepartment of Nephrology, Second Xiangya Hospital, Central South University, Changsha, Hunan, 410011, China. sunlinnwu11@163.com.
Second Xiangya Hospital of Central South University · CNCentral South University · CNNorthwestern University · US

Funding

Pathogenesis of Diabetic NephropathyR01DK060635 · NIDDK · NORTHWESTERN UNIVERSITY AT CHICAGO · PI QUAGGIN, SUSAN E. · 2002 to 2023
$6.6M
NIDDK NIH HHS DK60635NIDDK NIH HHS R01 DK060635
6 · The paper itself

Abstract

backgroundTransforming growth factor-β1 (TGF-β1) plays a key role in mesothelial-to-mesenchymal transition (MMT) during peritoneal dialysis (PD). However, the role of Akt in MMT transformation in PD is not clear.

resultsIn this study, we observed that the phosphorylated form of protein kinase B (Akt), termed as pAkt, was up-regulated in the peritoneum of mice undergoing PD. It was associated with thickening of the peritoneum and up-regulation of TGF-β1. Upregulation of pAkt paralleled with the increased expression of Smad ubiquitination regulatory factor 2 (Smurf2), Vimentin and fibronectin (FN), and decreased expression of mothers against decapentaplegic homolog 7 (Smad7) and Zonula Occludens protein 1(ZO-1) in mice undergoing PD treatment and in TGF-β1 induced human peritoneal mesothelial cells (HPMCs). These changes were reversed with the treatment of a PI3K/Akt inhibitor LY294002 in vivo or in cells transfected with Akt dominant-negative (Akt-DN) plasmids in vitro. Increased Smurf2 expression in HPMCs, induced by TGF-β1 was accompanied with altered expression of Transforming growth factor receptor I (TβR-I), Smad7, ZO-1, Vimentin and FN via Akt modulation. In addition, inhibition of Ubiquitin carboxyl-terminal hydrolase 4 (USP4) decreased TGF- β1-induced expression of TβR-I and reversed the altered expression of Smad7, Smurf2, ZO-1 and Vimentin. Moreover, TGF-β1 accentuated the interactions between Smurf2 and Smad7, while reduced the association between TβR-I and Smurf2. These interactions were reversed by the treatment of Akt-DN and USP4 siRNA, respectively.

conclusionsThese data implied that Akt mediated MMT in PD via Smurf2 modulation/and or Smad7 degradation while conceivably maintaining the TβRI stability, most likely by the USP4.

Indexed as

AnimalsCell LineChromonesDown-RegulationEpithelial CellsEpithelial-Mesenchymal TransitionFemaleFibronectinsHumansMiceMorpholinesPeritoneal DialysisPeritoneumPhosphatidylinositol 3-KinasesPhosphoinositide-3 Kinase InhibitorsProto-Oncogene Proteins2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-oneChromonesFibronectinsMorpholinesPhosphatidylinositol 3-KinasesPhosphoinositide-3 Kinase InhibitorsProto-Oncogene ProteinsProto-Oncogene Proteins c-aktSmad7 ProteinSmurf2 protein, mouseTjp1 protein, mouseTransforming Growth Factor beta1Ubiquitin-Protein LigasesUbiquitin-Specific ProteasesUbiquitin ThiolesteraseUsp4 protein, mouseVimentinZonula Occludens-1 Protein

Identifiers

PMID25885904
PMCPMC4369877
OpenAlexW2158921455

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.