Evidence map›Paper›PMID 37463911›Full record

ArticleNature communications2023

HCK induces macrophage activation to promote renal inflammation and fibrosis via suppression of autophagy.

Man Chen, Madhav C Menon, Wenlin Wang, Jia Fu, Zhengzi Yi, Zeguo Sun, Jessica Liu, Zhengzhe Li, Lingyun Mou, Khadija Banu and 9 more

Open access · goldAbstract read
In one paragraph

Article in Nature communications, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 69 papers.

0numbers the graph read from it
0cells of the map it votes in
69citing papers in PubMed
18.3field-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

69 citing papers in PubMed, 90 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
  4. Article
  5. The Src-Family Kinases Hck, Fgr and Lyn Drive Immune Complex-Mediated Glomerulonephritis Through the Syk Tyrosine Kinase.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026
    Article
  6. Article
  7. Article
  8. Review
  9. Article
  10. Article
  11. Article
  12. Article
  13. Article
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  15. Macrophage RNA polymerase II subunit 5-mediating protein deficiency exacerbates kidney inflammation and fibrosis.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2026
    Article
  16. Article
  17. Article
  18. Article
  19. Macrophage Actin Cytoskeleton in Chronic Rejection.Results and problems in cell differentiation · 2026
    Review
  20. Article

9 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

19 authors at 5 institutions in 2 countries.

Man ChenDivision of Nephrology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Madhav C MenonDivision of Nephrology, Yale School of Medicine, New Haven, CT, USA.
Wenlin WangDivision of Nephrology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Jia FuDivision of Nephrology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA.ORCID 0000-0002-8280-3813
Zhengzi YiDivision of Nephrology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Zeguo SunDivision of Nephrology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Jessica LiuDivision of Nephrology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Zhengzhe LiDivision of Nephrology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Lingyun MouDivision of Nephrology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA.ORCID 0000-0002-1328-5776
Khadija BanuDivision of Nephrology, Yale School of Medicine, New Haven, CT, USA.ORCID 0000-0001-6680-2688
Sui-Wan LeeCenter for Comparative Medicine and Surgery, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Ying DaiCenter for Comparative Medicine and Surgery, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Nanditha AnandakrishnanDivision of Nephrology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA.ORCID 0000-0003-2452-2527
Evren U AzelogluDivision of Nephrology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA.ORCID 0000-0001-6137-109X
Kyung LeeDivision of Nephrology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA.ORCID 0000-0002-9756-1765
Weijia ZhangDivision of Nephrology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Bhaskar DasArnold and Marie Schwartz College of Pharmacy and Health Sciences, Long Island University, Brooklyn, NY, USA. Bhaskar.Das@liu.edu.
John Cijiang HeDivision of Nephrology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA. Cijiang.he@mssm.edu.ORCID 0000-0002-1502-2849
Chengguo WeiDivision of Nephrology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA. Chengguo.wei@mssm.edu.ORCID 0000-0002-7940-8310
Icahn School of Medicine at Mount Sinai · USYale University · USJames J. Peters VA Medical Center · USLong Island University · USShandong Provincial Hospital · CN

Funding

Yale Clinical and Translational Science Award (U Component)UL1TR001863 · NCATS · YALE UNIVERSITY · PI John H. Krystal, LUCILA OHNO-MACHADO · 2016 to 2026
$102.9M
VIRAL PATHOGENESIS OF HIV ASSOCIATED NEPHROPATHYP01DK056492 · NIDDK · MOUNT SINAI SCHOOL OF MEDICINE OF NYU · PI KLOTMAN, PAUL EVAN · 1999 to 2021
$27.8M
Role of RTN1A in the Progression of Diabetic NephropathyR01DK109683 · NIDDK · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI HE, JOHN CIJIANG · 2016 to 2023
$3.3M
PP2A as a drug target for diabetic kidney diseaseR01DK122980 · NIDDK · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI HE, JOHN CIJIANG, LIU, RUIJIE · 2020 to 2024
$2.9M
Dichotomous roles of Shroom3 in Tubular cells and Podocytes in native and allograft kidneysR01DK122164 · NIDDK · YALE UNIVERSITY · PI Madhav C Menon · 2019 to 2026
$2.7M
The Role of LRG1 in Diabetic Kidney DiseaseR01DK117913 · NIDDK · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI Bhaskar Chandra Das, Kyung Lee · 2018 to 2026
$2.6M
Role of AMP-kinase pathway in the regulation of Minimal change disease-to-FSGS transitionR01DK132274 · NIDDK · YALE UNIVERSITY · PI Madhav C Menon · 2023 to 2026
$2.1M
Role of RARRES1 in diabetic kidney diseaseR01DK129467 · NIDDK · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI HE, JOHN CIJIANG, LEE, KYUNG · 2021 to 2024
$1.8M
Role of GPR56 in glomerular endothelial cell injury in early diabetic kidney diseaseK01DK125614 · NIDDK · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI FU, JIA · 2021 to 2025
$696k
Modelling mechanisms of progressive chronic kidney disease in APOL1 high-risk live-donors using BAC-Transgenic miceR21AI178705 · NIAID · YALE UNIVERSITY · PI ISHIBE, SHUTA, MENON, MADHAV C · 2023 to 2024
$461k
Role of Protein S in early Diabetic Kidney DiseaseI01BX000345 · VA · JAMES J PETERS VA MEDICAL CENTER · PI HE, JOHN CIJIANG · 2009 to 2024
–
BLRD VA I01 BX000345NCATS NIH HHS UL1 TR001863NIAID NIH HHS R21 AI178705NIDDK NIH HHS K01 DK125614NIDDK NIH HHS P01 DK056492NIDDK NIH HHS R01 DK109683NIDDK NIH HHS R01 DK117913NIDDK NIH HHS R01 DK122164NIDDK NIH HHS R01 DK122980NIDDK NIH HHS R01 DK129467NIDDK NIH HHS R01 DK132274
6 · The paper itself

Abstract

Renal inflammation and fibrosis are the common pathways leading to progressive chronic kidney disease (CKD). We previously identified hematopoietic cell kinase (HCK) as upregulated in human chronic allograft injury promoting kidney fibrosis; however, the cellular source and molecular mechanisms are unclear. Here, using immunostaining and single cell sequencing data, we show that HCK expression is highly enriched in pro-inflammatory macrophages in diseased kidneys. HCK-knockout (KO) or HCK-inhibitor decreases macrophage M1-like pro-inflammatory polarization, proliferation, and migration in RAW264.7 cells and bone marrow-derived macrophages (BMDM). We identify an interaction between HCK and ATG2A and CBL, two autophagy-related proteins, inhibiting autophagy flux in macrophages. In vivo, both global or myeloid cell specific HCK-KO attenuates renal inflammation and fibrosis with reduces macrophage numbers, pro-inflammatory polarization and migration into unilateral ureteral obstruction (UUO) kidneys and unilateral ischemia reperfusion injury (IRI) models. Finally, we developed a selective boron containing HCK inhibitor which can reduce macrophage pro-inflammatory activity, proliferation, and migration in vitro, and attenuate kidney fibrosis in the UUO mice. The current study elucidates mechanisms downstream of HCK regulating macrophage activation and polarization via autophagy in CKD and identifies that selective HCK inhibitors could be potentially developed as a new therapy for renal fibrosis.

Indexed as

NephritisRenal Insufficiency, ChronicUreteral ObstructionAnimalsAutophagyFibrosisHumansInflammationKidneyMacrophage ActivationMiceMice, Inbred C57BLProto-Oncogene Proteins c-hckHCK protein, humanHck protein, mouseProto-Oncogene Proteins c-hck

Identifiers

PMID37463911
PMCPMC10354075
OpenAlexW4384664327

What OpenQuestion holds

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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.