Evidence mapPaperPMID 35709763Full record

ArticleCell metabolism2022

Mapping the single-cell transcriptomic response of murine diabetic kidney disease to therapies.

Haojia Wu, Romer Gonzalez Villalobos, Xiang Yao, Dermot Reilly, Tao Chen, Matthew Rankin, Eugene Myshkin, Matthew D Breyer, Benjamin D Humphreys

Open access · bronzeAbstract read
In one paragraph

Article in Cell metabolism, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 151 papers.

0numbers the graph read from it
0cells of the map it votes in
151citing papers in PubMed
19.1field-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

151 citing papers in PubMed, 232 citations in OpenAlex.

  1. How do SGLT2 inhibitors protect the kidney? A mediation analysis of the EMPA-REG OUTCOME trial.Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association · 2024
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  14. Evolving Understanding of RNA Biology in Kidney Disease.Journal of the American Society of Nephrology : JASN · 2026
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91 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

9 authors at 2 institutions in 1 country.

Haojia WuDivision of Nephrology, Department of Medicine, Washington University, St. Louis, MO, USA.
Romer Gonzalez VillalobosCVM Janssen Research & Development, Boston, MA, USA.
Xiang YaoTox LJ Janssen Research & Development, La Jolla, CA, USA.
Dermot ReillyCVM Janssen Research & Development, Boston, MA, USA.
Tao ChenPSTS Janssen Research & Development, Shanghai, China.
Matthew RankinCVM Janssen Research & Development, Boston, MA, USA.
Eugene MyshkinCVM Janssen Research & Development, Boston, MA, USA.
Matthew D BreyerCVM Janssen Research & Development, Boston, MA, USA.
Benjamin D HumphreysDivision of Nephrology, Department of Medicine, Washington University, St. Louis, MO, USA; Department of Developmental Biology, Washington University, St. Louis, MO, USA. Electronic address: humphreysbd@wustl.edu.
Janssen (United States) · USWashington University in St. Louis · US

Funding

TRANSGENICS COREP60DK020579 · WASHINGTON UNIVERSITY · 1986 to 2005
$11.8M
WU P&FP30DK020579 · NIDDK · WASHINGTON UNIVERSITY · 2022 to 2025
$5.6M
NIDDK NIH HHS P30 DK020579NIDDK NIH HHS P60 DK020579NIDDK NIH HHS R01 DK103740NIDDK NIH HHS UC2 DK126024
6 · The paper itself

Abstract

Diabetic kidney disease (DKD) occurs in ∼40% of patients with diabetes and causes kidney failure, cardiovascular disease, and premature death. We analyzed the response of a murine DKD model to five treatment regimens using single-cell RNA sequencing (scRNA-seq). Our atlas of ∼1 million cells revealed a heterogeneous response of all kidney cell types both to DKD and its treatment. Both monotherapy and combination therapies targeted differing cell types and induced distinct and non-overlapping transcriptional changes. The early effects of sodium-glucose cotransporter-2 inhibitors (SGLT2i) on the S1 segment of the proximal tubule suggest that this drug class induces fasting mimicry and hypoxia responses. Diabetes downregulated the spliceosome regulator serine/arginine-rich splicing factor 7 (Srsf7) in proximal tubule that was specifically rescued by SGLT2i. In vitro proximal tubule knockdown of Srsf7 induced a pro-inflammatory phenotype, implicating alternative splicing as a driver of DKD and suggesting SGLT2i regulation of proximal tubule alternative splicing as a potential mechanism of action for this drug class.

Indexed as

Cardiovascular DiseasesDiabetes Mellitus, Type 2Diabetic NephropathiesSodium-Glucose Transporter 2 InhibitorsAnimalsMiceTranscriptomeSodium-Glucose Transporter 2 InhibitorsACEichronic kidney diseasediabetesdrug responseFSGShypertensionkidneyrosiglitazoneSGLT2isingle-cell RNA-seqT2D

Identifiers

PMID35709763
PMCPMC9262852
OpenAlexW4282982919

What Socratic holds

Textmetadata
LicenceTDM
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 Socratic graph.