Evidence map›Paper›PMID 26022003›Full record

ArticleThe Journal of pharmacology and experimental therapeutics2015

Activation of Sirtuin-1 Promotes Renal Fibroblast Activation and Aggravates Renal Fibrogenesis.

Murugavel Ponnusamy, Michelle A Zhuang, Xiaoxu Zhou, Evelyn Tolbert, George Bayliss, Ting C Zhao, Shougang Zhuang

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

Article in The Journal of pharmacology and experimental therapeutics, 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
0.9field-weighted citation impact, top 23% 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. Review
  2. Review
  3. Role of epigenetics in corneal health and disease.Progress in retinal and eye research · 2025
    Review
  4. Review
  5. Article
  6. Article
  7. Review
  8. The roles of sirtuins in ferroptosis.Frontiers in physiology · 2023
    Review
  9. Article
  10. Article
  11. Article
  12. Article
  13. Article
  14. Review
  15. Review
  16. TGF-β: the master regulator of fibrosis.Nature reviews. Nephrology · 2016
    Review
  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

7 authors at 3 institutions in 2 countries.

Murugavel PonnusamyDepartment of Medicine, Rhode Island Hospital and Alpert Medical School, Brown University, Providence, Rhode Island (M.P., M.A.Z., X.Z., E.T., G.B., S.Z.); Department of Surgery, Roger William Medical Center, Boston University Medical School, Providence, Rhode Island (T.C.Z.); and Department of Nephrology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China (S.Z.).
Michelle A ZhuangDepartment of Medicine, Rhode Island Hospital and Alpert Medical School, Brown University, Providence, Rhode Island (M.P., M.A.Z., X.Z., E.T., G.B., S.Z.); Department of Surgery, Roger William Medical Center, Boston University Medical School, Providence, Rhode Island (T.C.Z.); and Department of Nephrology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China (S.Z.).
Xiaoxu ZhouDepartment of Medicine, Rhode Island Hospital and Alpert Medical School, Brown University, Providence, Rhode Island (M.P., M.A.Z., X.Z., E.T., G.B., S.Z.); Department of Surgery, Roger William Medical Center, Boston University Medical School, Providence, Rhode Island (T.C.Z.); and Department of Nephrology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China (S.Z.).
Evelyn TolbertDepartment of Medicine, Rhode Island Hospital and Alpert Medical School, Brown University, Providence, Rhode Island (M.P., M.A.Z., X.Z., E.T., G.B., S.Z.); Department of Surgery, Roger William Medical Center, Boston University Medical School, Providence, Rhode Island (T.C.Z.); and Department of Nephrology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China (S.Z.).
George BaylissDepartment of Medicine, Rhode Island Hospital and Alpert Medical School, Brown University, Providence, Rhode Island (M.P., M.A.Z., X.Z., E.T., G.B., S.Z.); Department of Surgery, Roger William Medical Center, Boston University Medical School, Providence, Rhode Island (T.C.Z.); and Department of Nephrology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China (S.Z.).
Ting C ZhaoDepartment of Medicine, Rhode Island Hospital and Alpert Medical School, Brown University, Providence, Rhode Island (M.P., M.A.Z., X.Z., E.T., G.B., S.Z.); Department of Surgery, Roger William Medical Center, Boston University Medical School, Providence, Rhode Island (T.C.Z.); and Department of Nephrology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China (S.Z.).
Shougang ZhuangDepartment of Medicine, Rhode Island Hospital and Alpert Medical School, Brown University, Providence, Rhode Island (M.P., M.A.Z., X.Z., E.T., G.B., S.Z.); Department of Surgery, Roger William Medical Center, Boston University Medical School, Providence, Rhode Island (T.C.Z.); and Department of Nephrology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China (S.Z.) szhuang@lifespan.org.
Brown University · USProvidence College · USShanghai East Hospital · CN

Funding

Histone deacetylases as novel therapeutic targets for kidney fibrosisR01DK085065 · NIDDK · RHODE ISLAND HOSPITAL · PI ZHUANG, SHOUGANG · 2010 to 2017
$2.8M
NIDDK NIH HHS 5R01-DK085065NIDDK NIH HHS R01 DK085065
6 · The paper itself

Abstract

Although activation of sirtuin-1 (SIRT1) has been shown to protect the kidney from acute injury, its role in renal fibrosis remains controversial since both inhibition and activation of SIRT1 have been reported to attenuate renal fibrosis. To resolve this conflict, we further examined the effect of SIRT1 activators on the activation of renal interstitial fibroblasts and development of renal fibrosis in vivo and in vitro. In a murine model of renal fibrosis induced by unilateral ureteral obstruction, administration of SRT1720 (N-[2-[3-(piperazin-1-ylmethyl)imidazo[2,1-b][1,3]thiazol-6-yl]phenyl]quinoxaline-2-carboxamide), a potent activator of SIRT1, accelerated deposition of collagen fibrils and increased expression of fibroblast activation markers (α-smooth muscle actin [α-SMA], collagen I, and fibronectin) in the obstructive kidney of mice. In cultured rat renal interstitial fibroblasts (NRK-49F), exposure of cells to SRT1720 or YK-3-237 (B-[2-methoxy-5-[(1E)-3-oxo-3-(3,4,5-trimethoxyphenyl)-1-propen-1-yl]phenyl]-boronic acid), another SIRT1 activator, also resulted in enhanced expression of α-SMA and fibronectin. Mechanistic studies showed that augmentation of renal fibrogenesis by SRT1720 is associated with elevated phosphorylation of epidermal growth factor receptor (EGFR) and platelet-derived growth factor receptor β (PDGFRβ). SRT1720 treatment also increased the phosphorylation of signal transducer and activator of transcription 3 and protein kinase B in the fibrotic kidney and NRK-49F cells. However, SRT1720 treatment did not affect expression of proliferating cell nuclear protein, a proliferation marker and activation of extracellular signal regulated kinase 1/2 in vitro and in vivo. These results indicate that SIRT1-activating compounds can provoke renal fibrogenesis through a mechanism involved in the activation of EGFR and PDGFR signaling pathways and suggest that long-term use of SIRT1 activators risks the development and progression of chronic kidney disease.

Indexed as

AnimalsCells, CulturedFibroblastsFibrosisKidneyKidney DiseasesMaleMiceMice, Inbred C57BLRatsSirtuin 1Sirt1 protein, mouseSirtuin 1

Identifiers

PMID26022003
PMCPMC4518074
OpenAlexW2284830399

What OpenQuestion holds

Textmetadata
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.