Evidence map›Paper›PMID 36008138›Full record

ArticleGenes & development2022

KLF5 governs sphingolipid metabolism and barrier function of the skin.

Ying Lyu, Yinglu Guan, Lisa Deliu, Ericka Humphrey, Joanna K Frontera, Youn Joo Yang, Daniel Zamler, Kun Hee Kim, Vakul Mohanty, Kevin Jin and 16 more

Open access · diamondAbstract read
In one paragraph

Article in Genes & development, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.

0numbers the graph read from it
0cells of the map it votes in
17citing papers in PubMed
–field-weighted citation impact
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

17 citing papers in PubMed, 23 citations in OpenAlex.

  1. Review
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  3. Article
  4. Review
  5. Article
  6. Article
  7. Article
  8. Article
  9. Hidradenitis Suppurativa Tunnels: Unveiling a Unique Disease Entity.JID innovations : skin science from molecules to population health · 2025
    Review
  10. Article
  11. Article
  12. Article
  13. Article
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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

26 authors at 2 institutions in 1 country.

Ying Lyu *Department of Cancer Biology, University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.
Yinglu Guan *Department of Cancer Biology, University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.
Lisa DeliuDepartment of Cancer Biology, University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.
Ericka HumphreyDepartment of Cancer Biology, University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.
Joanna K FronteraDepartment of Cancer Biology, University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.
Youn Joo YangDepartment of Cancer Biology, University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.
Daniel ZamlerDepartment of Cancer Biology, University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.
Kun Hee KimDepartment of Bioinformatics and Computational Biology, University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.
Vakul MohantyDepartment of Bioinformatics and Computational Biology, University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.
Kevin JinDepartment of Cancer Biology, University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.ORCID http://orcid.org/0000-0003-3924-8620
Vakul MohantyDepartment of Cancer Biology, University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.
Virginia LiuDepartment of Cancer Biology, University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.
Jinzhuang DouDepartment of Bioinformatics and Computational Biology, University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.
Lucas J VeillonDepartment of Bioinformatics and Computational Biology, University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.
Shwetha V KumarDepartment of Bioinformatics and Computational Biology, University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.
Philip L LorenziDepartment of Bioinformatics and Computational Biology, University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.
Yang ChenDepartment of Cancer Biology, University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.
Kathleen M McAndrewsDepartment of Cancer Biology, University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.
Sergei GrivennikovDepartment of Medicine, Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, California 90048, USA.
Xingzhi SongDepartment of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.
Jianhua ZhangDepartment of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.
Yuanxin XiDepartment of Bioinformatics and Computational Biology, University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.
Jing WangDepartment of Bioinformatics and Computational Biology, University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.
Ken ChenDepartment of Bioinformatics and Computational Biology, University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.
Priyadharsini NagarajanDepartment of Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.
Yejing GeDepartment of Cancer Biology, University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.
The University of Texas MD Anderson Cancer Center · USCedars-Sinai Medical Center · US

Funding

TRANSLATIONAL AND ANALYTICAL CHEMISTRY COREP30CA016672 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI PETER W PISTERS · 1985 to 2026
$279.3M
Orbitrap Elite High-Resolution Mass Spectrometer for Proteomics and MetabolomicsS10OD012304 · OD · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI HAWKE, DAVID H · 2013 to 2013
$877k
Dissect stress response in skin epithelial wounding and hyperproliferative disordersK01AR072132 · NIAMS · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI GE, YEJING · 2018 to 2022
$673k
NCI NIH HHS P30 CA016672NIAMS NIH HHS K01 AR072132NIH HHS S10 OD012304
6 · The paper itself

Abstract

Stem cells are fundamental units of tissue remodeling whose functions are dictated by lineage-specific transcription factors. Home to epidermal stem cells and their upward-stratifying progenies, skin relies on its secretory functions to form the outermost protective barrier, of which a transcriptional orchestrator has been elusive. KLF5 is a Krüppel-like transcription factor broadly involved in development and regeneration whose lineage specificity, if any, remains unclear. Here we report KLF5 specifically marks the epidermis, and its deletion leads to skin barrier dysfunction in vivo. Lipid envelopes and secretory lamellar bodies are defective in KLF5-deficient skin, accompanied by preferential loss of complex sphingolipids. KLF5 binds to and transcriptionally regulates genes encoding rate-limiting sphingolipid metabolism enzymes. Remarkably, skin barrier defects elicited by KLF5 ablation can be rescued by dietary interventions. Finally, we found that KLF5 is widely suppressed in human diseases with disrupted epidermal secretion, and its regulation of sphingolipid metabolism is conserved in human skin. Altogether, we established KLF5 as a disease-relevant transcription factor governing sphingolipid metabolism and barrier function in the skin, likely representing a long-sought secretory lineage-defining factor across tissue types.

Indexed as

barriersecretoryskin epidermissphingolipid metabolismstem cellstranscription factors

Identifiers

PMID36008138
PMCPMC9480852
OpenAlexW4293243049

What Socratic holds

Textmetadata
LicenceCC BY-NC
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.