Evidence map›Paper›PMID 34941574›Full record

ArticleJCI insight2022

DDR1 contributes to kidney inflammation and fibrosis by promoting the phosphorylation of BCR and STAT3.

Corina M Borza, Gema Bolas, Fabian Bock, Xiuqi Zhang, Favour C Akabogu, Ming-Zhi Zhang, Mark de Caestecker, Min Yang, Haichun Yang, Ethan Lee and 5 more

Open access · goldAbstract read
In one paragraph

Article in JCI insight, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.

0numbers the graph read from it
0cells of the map it votes in
29citing papers in PubMed
4.3field-weighted citation impact, top 5% 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

29 citing papers in PubMed, 57 citations in OpenAlex.

  1. Trial
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  7. Annexin A13 Protects Against Acute Kidney Injury by Inactivating TGF-β/Smad3 Signaling.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
    Article
  8. Article
  9. Article
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  12. Rac1 promotes proximal tubule kidney repair by coupling the actin cytoskeleton to mitochondrial function.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  13. Article
  14. Article
  15. Review
  16. Integrins in the kidney - beyond the matrix.Nature reviews. Nephrology · 2025
    Review
  17. Review
  18. Article
  19. Review
  20. 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

15 authors at 4 institutions in 2 countries.

Corina M BorzaDepartment of Medicine, Division of Nephrology and Hypertension, and.
Gema BolasDepartment of Medicine, Division of Nephrology and Hypertension, and.
Fabian BockDepartment of Medicine, Division of Nephrology and Hypertension, and.
Xiuqi ZhangDepartment of Medicine, Division of Nephrology and Hypertension, and.
Favour C AkaboguDepartment of Medicine, Division of Nephrology and Hypertension, and.
Ming-Zhi ZhangDepartment of Medicine, Division of Nephrology and Hypertension, and.
Mark de CaesteckerDepartment of Medicine, Division of Nephrology and Hypertension, and.
Min YangDepartment of Medicine, Division of Nephrology and Hypertension, and.
Haichun YangDepartment of Pathology, Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.
Ethan LeeDepartment of Cell and Developmental Biology, Vanderbilt University, Nashville, Tennessee, USA.
Leslie GewinDivision of Nephrology, Washington University School of Medicine, St. Louis, Missouri, USA.
Agnes B FogoDepartment of Medicine, Division of Nephrology and Hypertension, and.
W Hayes McDonaldProteomics Laboratory, Mass Spectrometry Research Center, Vanderbilt University, Nashville, Tennessee, USA.
Roy ZentDepartment of Medicine, Division of Nephrology and Hypertension, and.
Ambra PozziDepartment of Medicine, Division of Nephrology and Hypertension, and.
Hypertension Institute · USVanderbilt University · USNashville VA Medical Center · USWashington University in St. Louis · US

Funding

The Role of the EGF Receptor in Acute and Chronic Renal InjuryR01DK051265 · NIDDK · VANDERBILT UNIVERSITY MEDICAL CENTER · PI RAYMOND C. HARRIS, Mingzhi Zhang · 1997 to 2026
$10.1M
The Laminin Receptors in Kidney FibrosisR01DK069921 · NIDDK · VANDERBILT UNIVERSITY MEDICAL CENTER · PI ROY ZENT · 2005 to 2026
$9.5M
The Role of renal macrophages in recovery from renal injuryR01DK095785 · NIDDK · VANDERBILT UNIVERSITY MEDICAL CENTER · PI RAYMOND C. HARRIS, Mingzhi Zhang · 2013 to 2026
$6.7M
Vanderbilt O'Brien Kidney Center - Core D - Clinical and Translational CoreP30DK114809 · NIDDK · VANDERBILT UNIVERSITY MEDICAL CENTER · PI DE CAESTECKER, MARK P. · 2017 to 2021
$5.9M
Mechanism of Wnt signal transductionR35GM122516 · NIGMS · VANDERBILT UNIVERSITY · PI ETHAN LEE · 2017 to 2026
$5.8M
TGF-beta Pathways that Protect Epithelia in Chronic Renal InjuryR01DK108968 · NIDDK · WASHINGTON UNIVERSITY · PI GEWIN, LESLIE S · 2016 to 2025
$3.7M
Prune Belly Syndrome: Mechanisms of Filamin A MutationsR01DK127589 · NIDDK · UT SOUTHWESTERN MEDICAL CENTER · PI BAKER, LINDA A., QIN, JUN · 2020 to 2024
$2.5M
Matrix receptors in chronic kidney diseaseR01DK119212 · NIDDK · VANDERBILT UNIVERSITY MEDICAL CENTER · PI BORZA, CORINA MARILENA, POZZI, AMBRA · 2018 to 2022
$1.7M
Mechanisms and therapeutic manipulation of retinoic acid signaling in Acute Kidney InjuryR01DK112688 · NIDDK · VANDERBILT UNIVERSITY MEDICAL CENTER · PI DE CAESTECKER, MARK P. · 2017 to 2020
$1.7M
Role of Collagen Binding Receptors in GlomerulosclerosisI01BX002025 · VA · VETERANS HEALTH ADMINISTRATION · PI AMBRA POZZI · 2013 to 2026
–
The Role of Fatty Acid Oxidation in Injured Kidney TubulesI01BX003425 · VA · VETERANS HEALTH ADMINISTRATION · PI Leslie S Gewin · 2018 to 2026
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The ILK/PINCH/Parvin complex in renal tubulogenesisI01BX002196 · VA · VETERANS HEALTH ADMINISTRATION · PI ZENT, ROY · 2013 to 2025
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BLRD VA I01 BX000320BLRD VA I01 BX002025BLRD VA I01 BX002196BLRD VA I01 BX003425BLRD VA IK6 BX005240NIDDK NIH HHS P30 DK114809NIDDK NIH HHS R01 DK051265NIDDK NIH HHS R01 DK069921NIDDK NIH HHS R01 DK095785NIDDK NIH HHS R01 DK108968NIDDK NIH HHS R01 DK112688NIDDK NIH HHS R01 DK119212NIDDK NIH HHS R01 DK127589NIGMS NIH HHS R35 GM122516
6 · The paper itself

Abstract

Discoidin domain receptor 1 (DDR1), a receptor tyrosine kinase activated by collagen, contributes to chronic kidney disease. However, its role in acute kidney injury and subsequent development of kidney fibrosis is not clear. Thus, we performed a model of severe ischemia/reperfusion-induced acute kidney injury that progressed to kidney fibrosis in WT and Ddr1-null mice. We showed that Ddr1-null mice had reduced acute tubular injury, inflammation, and tubulointerstitial fibrosis with overall decreased renal monocyte chemoattractant protein (MCP-1) levels and STAT3 activation. We identified breakpoint cluster region (BCR) protein as a phosphorylated target of DDR1 that controls MCP-1 production in renal proximal tubule epithelial cells. DDR1-induced BCR phosphorylation or BCR downregulation increased MCP-1 secretion, suggesting that BCR negatively regulates the levels of MCP-1. Mechanistically, phosphorylation or downregulation of BCR increased β-catenin activity and in turn MCP-1 production. Finally, we showed that DDR1-mediated STAT3 activation was required to stimulate the secretion of TGF-β. Thus, DDR1 contributes to acute and chronic kidney injury by regulating BCR and STAT3 phosphorylation and in turn the production of MCP-1 and TGF-β. These findings identify DDR1 an attractive therapeutic target for ameliorating both proinflammatory and profibrotic signaling in kidney disease.

Indexed as

Gene Expression RegulationAcute Kidney InjuryAnimalsCell LineCells, CulturedDiscoidin Domain Receptor 1FemaleFibrosisInflammationKidney Tubules, ProximalMaleMiceMice, KnockoutPhosphorylationProto-Oncogene Proteins c-bcrRNABcr protein, mouseDdr1 protein, mouseDiscoidin Domain Receptor 1Proto-Oncogene Proteins c-bcrRNAStat3 protein, mouseSTAT3 Transcription FactorCell BiologyFibrosisNephrology

Identifiers

PMID34941574
PMCPMC8855801
OpenAlexW4200301351

What OpenQuestion holds

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LicenceCC BY
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Registered trials

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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.