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Cited by 47Chronic Kidney Disease and DiabetesAcute Kidney Injury ResearchCytokine Signaling Pathways and Interactions

Deletion of STAT3 from Foxd1 cell population protects mice from kidney fibrosis by inhibiting pericytes trans-differentiation and migration

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Ajay, Amrendra K., Zhao, Li, Vig, Shruti, Fujiwara, Mai, Thakurela, Sudhir, Jadhav, Shreyas, Cho, Andrew, Chiu, I-Jen +13 more·2022·Cell Reports
DOI 10.1016/j.celrep.2022.110473PMC PMC10027389
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Abstract

Signal transduction and activator of transcription 3 (STAT3) is a key transcription factor implicated in the pathogenesis of kidney fibrosis. Although Stat3 deletion in tubular epithelial cells is known to protect mice from fibrosis, vFoxd1 cells remains unclear. Using Foxd1-mediated Stat3 knockout mice, CRISPR, and inhibitors of STAT3, we investigate its function. STAT3 is phosphorylated in tubular epithelial cells in acute kidney injury, whereas it is expanded to interstitial cells in fibrosis in mice and humans. Foxd1-mediated deletion of Stat3 protects mice from folic-acid- and aristolochic-acid-induced kidney fibrosis. Mechanistically, STAT3 upregulates the inflammation and differentiates pericytes into myofibroblasts. STAT3 activation increases migration and profibrotic signaling in genome-edited, pericyte-like cells. Conversely, blocking Stat3 inhibits detachment, migration, and profibrotic signaling. Furthermore, STAT3 binds to the Collagen1a1 promoter in mouse kidneys and cells. Together, our study identifies a previously unknown function of STAT3 that promotes kidney fibrosis and has therapeutic value in fibrosis.

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  • Activated STAT3 can regulate transcription of many target genes involved in cell proliferation, migration, differentiation, and apoptosis.

    “Activated STAT3 can regulate the transcription of many target genes involved in cell proliferation, migration, differentiation, and apoptosis [28, 45].”

    From Saikosaponin b1 Attenuates Liver Fibrosis by Blocking STAT3/Gli1 Interaction and Inducing Gli1 Degradation (2025) · cites this paper as [45]

    The Introduction says STAT3 initiates transcriptional programs, and the Results report effects of activated STAT3 on pericyte proliferation and migration. The Results also identify Collagen1a1 as a direct transcriptional target involved in fibrotic signaling. These passages do not establish the full claimed range of target genes, particularly genes involved in apoptosis. (LLM, conf=0.85)

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Authors
Ajay, A. K., Zhao, L., Vig, S., Fujiwara, M., Thakurela, S., Jadhav, S., Cho, A., Chiu, I.-J., Ding, Y., Ramachandran, K., Mithal, A., Bhatt, A., Chaluvadi, P., Gupta, M. K., Shah, S. I., Sabbisetti, V. S., Waaga-Gasser, A. M., Frank, D. A., Murugaiyan, G., Bonventre, J. V., & Hsiao, L.-L.
Affiliations
  • Brigham and Women's Hospital (US)
  • Broad Institute (US)
  • Joslin Diabetes Center (US)
Corresponding author
  • Ajay, Amrendra K.
  • Hsiao, Li-Li
ORCID
Venue
Cell Reports
Publisher
Elsevier BV
Published
2022-03
Volume
38
Issue
10
Pages
110473
ISSN
2211-1247 (ISSN-L)
DOI
10.1016/j.celrep.2022.110473
PMC
PMC10027389
OpenAlex
W4220984477
Cited by
47
References
3
Citations by year
2026: 9 · 2025: 8 · 2024: 11 · 2023: 16 · 2022: 3
FWCI
6.03
Type
journal article
Language
en
Open access
Licence
Locations
  • Cell Reports (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • National Science Foundation
  • American Heart Association (19CDA34780005)
  • National Institutes of Health (UH3TR002155, AI435801)
  • National Cancer Institute
  • National Institute of Allergy and Infectious Diseases (R01AI151953)
  • National Institute of Diabetes and Digestive and Kidney Diseases (R37DK039773, R01DK039773)
  • National Center for Advancing Translational Sciences
Topics
  • Health Sciences › Medicine › Nephrology › Chronic Kidney Disease and Diabetes
  • Health Sciences › Medicine › Nephrology › Acute Kidney Injury Research
  • Health Sciences › Medicine › Oncology › Cytokine Signaling Pathways and Interactions
Keywords
STAT3, renal fibrosis, FOXD1, pericytes, myofibroblast differentiation, cell migration, tubular epithelial cells, aristolochic acid nephropathy, STAT3 inhibitor, acute kidney injury, interstitial fibrosis
MeSH terms
Animals, Fibrosis, Kidney, Mice, Inbred C57BL, Signal Transduction, Mice, Knockout, Pericytes, STAT3 Transcription Factor, Mice, Forkhead Transcription Factors, Cell Transdifferentiation, Acute Kidney Injury

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

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