Evidence map›Paper›PMID 30614190›Full record

ArticleAging cell2019

Sirt1-hypoxia-inducible factor-1α interaction is a key mediator of tubulointerstitial damage in the aged kidney.

Dong Ryeol Ryu, Mi Ra Yu, Kyoung Hye Kong, Hyoungnae Kim, Soon Hyo Kwon, Jin Seok Jeon, Dong Cheol Han, Hyunjin Noh

Open access · goldAbstract read
In one paragraph

Article in Aging cell, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 72 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
72citing papers in PubMed, 1 pooled it
9.8field-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

72 citing papers in PubMed, 1 synthesis or guideline pooled it, 127 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Review
  4. Review
  5. Review
  6. Aging and cancer: current understandings and future perspectives.Signal transduction and targeted therapy · 2026
    Review
  7. Article
  8. Article
  9. Review
  10. Article
  11. The Yin-Yang balance of SIRT1 and SIRT2 in cancer metabolic remodeling.International journal of biological sciences · 2026
    Review
  12. Review
  13. Review
  14. Article
  15. Article
  16. Autophagy: The convergence point of aging and cancer.Biochemistry and biophysics reports · 2025
    Review
  17. Article
  18. The Role of Hypoxia in Longevity.Aging and disease · 2025
    Review
  19. Article
  20. Article

12 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

8 authors at 2 institutions in 1 country.

Dong Ryeol RyuSchool of Medicine, Ewha Womans University, Seoul, Korea.
Mi Ra YuHyonam Kidney Laboratory, Soon Chun Hyang University, Seoul, Korea.
Kyoung Hye KongSchool of Medicine, Ewha Womans University, Seoul, Korea.
Hyoungnae KimHyonam Kidney Laboratory, Soon Chun Hyang University, Seoul, Korea.
Soon Hyo KwonHyonam Kidney Laboratory, Soon Chun Hyang University, Seoul, Korea.
Jin Seok JeonHyonam Kidney Laboratory, Soon Chun Hyang University, Seoul, Korea.
Dong Cheol HanHyonam Kidney Laboratory, Soon Chun Hyang University, Seoul, Korea.
Hyunjin NohHyonam Kidney Laboratory, Soon Chun Hyang University, Seoul, Korea.ORCID 0000-0002-1904-1684
Soonchunhyang University · KREwha Womans University · KR

Funding

National Research Foundation of Korea Grant, funded by the Korean Government 2014R1A2A2A01004731National Research Foundation of Korea Grant, funded by the Korean Government 2017M3A9B4032528
6 · The paper itself

Abstract

Although it is known that the expression and activity of sirtuin 1 (Sirt1) decrease in the aged kidney, the role of interaction between Sirt1 and hypoxia-inducible factor (HIF)-1α is largely unknown. In this study, we investigated whether HIF-1α could be a deacetylation target of Sirt1 and the effect of their interaction on age-associated renal injury. Five-week-old (young) and 24-month-old (old) C57Bl/6J mice were assessed for their age-associated changes. Kidneys from aged mice showed increased infiltration of CD68-positive macrophages, higher expression of extracellular matrix (ECM) proteins, and more apoptosis than young controls. They also showed decreased Sirt1 expression along with increased acetylated HIF-1α. The level of Bcl-2/adenovirus E1B-interacting protein 3, carbonic anhydrase 9, Snail, and transforming growth factor-β1, which are regulated by HIF-1α, was significantly higher in aged mice suggesting that HIF-1α activity was increased. In HK-2 cells, Sirt1 inhibitor sirtinol and siRNA-mediated knockdown of Sirt1 enhanced apoptosis and ECM accumulation. During hypoxia, Sirt1 was down-regulated, which allowed the acetylation and activation of HIF-1α. Resveratrol, a Sirt1 activator, effectively prevented hypoxia-induced production of ECM proteins, mitochondrial damage, reactive oxygen species generation, and apoptosis. The inhibition of HIF-1α activity by Sirt1-induced deacetylation of HIF-1α was confirmed by Sirt1 overexpression under hypoxic conditions and by resveratrol treatment or Sirt1 overexpression in HIF-1α-transfected HK-2 cells. Finally, we confirmed that chronic activation of HIF-1α promoted apoptosis and fibrosis, using tubular cell-specific HIF-1α transgenic mice. Taken together, our data suggest that Sirt1-induced deacetylation of HIF-1α may have protective effects against tubulointerstitial damage in aged kidney.

Indexed as

AnimalsHypoxia-Inducible Factor 1, alpha SubunitMaleMiceMice, Inbred C57BLMice, TransgenicNephritis, InterstitialSirtuin 1Hif1a protein, mouseHypoxia-Inducible Factor 1, alpha SubunitSirt1 protein, mouseSirtuin 1agedeacetylationHIF-1αSirt1

Identifiers

PMID30614190
PMCPMC6413666
OpenAlexW2908906948

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.