Evidence map›Paper›PMID 20299359›Full record

ArticleJournal of the American Society of Nephrology : JASN2010

Reactive oxygen species promote caspase-12 expression and tubular apoptosis in diabetic nephropathy.

Marie-Luise Brezniceanu, Cara J Lau, Nicolas Godin, Isabelle Chénier, Alain Duclos, Jean Ethier, Janos G Filep, Julie R Ingelfinger, Shao-Ling Zhang, John S D Chan

Open access · greenAbstract read
In one paragraph

Article in Journal of the American Society of Nephrology : JASN, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.

0numbers the graph read from it
0cells of the map it votes in
47citing papers in PubMed
3.6field-weighted citation impact, top 7% 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

47 citing papers in PubMed, 105 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
  4. Review
  5. Observational
  6. Review
  7. Article
  8. Article
  9. Article
  10. Review
  11. Article
  12. Article
  13. Article
  14. Article
  15. Article
  16. Article
  17. Article
  18. Article
  19. Article
  20. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

10 authors at 1 institution in 1 country.

Marie-Luise BrezniceanuUniversité de Montréal, Centre de recherche du Centre hospitalier de l'Université de Montréal, Hôtel-Dieu Hospital, Pavillon Masson, 3850 Saint Urbain Street, Montréal, Québec, Canada H2W 1T8.
Cara J Lau
Nicolas Godin
Isabelle Chénier
Alain Duclos
Jean Ethier
Janos G Filep
Julie R Ingelfinger
Shao-Ling Zhang
John S D Chan
Centre Hospitalier de l’Université de Montréal · CA

Funding

ROLES OF THE PROXIMAL TUBULE RENIN ANGIOTENSIN SYSTEMR01HL048455 · NHLBI · MASSACHUSETTS GENERAL HOSPITAL · PI INGELFINGER, JULIE R. · 1992 to 2000
$295k
Canadian Institutes of Health Research MOP 84363Canadian Institutes of Health Research MOP 86450Canadian Institutes of Health Research MT-12573NHLBI NIH HHS HL-48455
6 · The paper itself

Abstract

Apoptosis of tubular epithelial cells contributes to the tubular atrophy that accompanies diabetic nephropathy. Reactive oxygen species (ROS) promote tubular apoptosis, but the mechanisms by which this occurs are incompletely understood. Here, we sought proapoptotic genes that ROS differentially upregulate in renal proximal tubular cells of diabetic (db/db) mice. We performed microarray analysis using total RNA from freshly isolated renal proximal tubules of nondiabetic, diabetic, and diabetic transgenic mice overexpressing catalase in the proximal tubule (thereby attenuating ROS). We observed greater expression of caspase-12 in the proximal tubules of the diabetic mice compared with the nondiabetic and diabetic transgenic mice. Quantitative PCR and immunohistochemistry confirmed the enhanced expression of caspase-12, as well as members of the endoplasmic reticulum stress-induced apoptotic pathway. Ex vivo, albumin induced caspase-12 activity and expression (protein and mRNA) and mRNA expression of the CCAT/enhancer-binding protein homologous protein in freshly isolated wild-type proximal tubules but not in catalase-overexpressing proximal tubules. In vitro, albumin stimulated activity of both caspase-12 and caspase-3 as well as expression of caspase-12 and CCAT/enhancer-binding protein homologous protein in a human proximal tubule cell line (HK-2). The free radical scavenger tiron inhibited these effects. Furthermore, knockdown of caspase-12 with small interfering RNA reduced albumin-induced apoptosis in HK-2 cells. Taken together, these studies demonstrate that albuminuria may induce tubular apoptosis through generation of ROS and the subsequent expression and activation of endoplasmic reticulum stress genes in the diabetic kidney.

Indexed as

ApoptosisAlbuminsAnimalsCaspase 12Cell LineDiabetic NephropathiesDisease Models, AnimalEndoplasmic ReticulumEndoplasmic Reticulum Chaperone BiPGene Expression RegulationHeat-Shock ProteinsHumansKidney Tubules, ProximalMaleMiceMice, Mutant StrainsAlbuminsCaspase 12Ddit3 protein, mouseEndoplasmic Reticulum Chaperone BiPHeat-Shock ProteinsReactive Oxygen SpeciesRNA, Small InterferingTranscription Factor CHOP

Identifiers

PMID20299359
PMCPMC2900966
OpenAlexW2118464825

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.