Evidence map›Paper›PMID 31220272›Full record

ArticleHuman molecular genetics2019

Altered keratinocyte differentiation is an early driver of keratin mutation-based palmoplantar keratoderma.

Abigail G Zieman, Brian G Poll, Jingqun Ma, Pierre A Coulombe

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Human molecular genetics, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.

0numbers the graph read from it
0cells of the map it votes in
24citing papers in PubMed
1.8field-weighted citation impact, top 17% 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

24 citing papers in PubMed, 34 citations in OpenAlex.

  1. Review
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  5. Article
  6. Intermediate filaments and their associated molecules.Journal of biomedical research · 2025
    Article
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  19. Article
  20. Intermediate filaments as effectors of differentiation.Current opinion in cell biology · 2021
    Review
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

4 authors at 2 institutions in 1 country.

Abigail G ZiemanDepartment of Biochemistry and Molecular Biology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, USA.
Brian G PollDepartment of Biochemistry and Molecular Biology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, USA.
Jingqun MaDepartment of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, MI, USA.
Pierre A CoulombeDepartment of Biochemistry and Molecular Biology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, USA.
Johns Hopkins University · USUniversity of Michigan · US

Funding

BIOCHEMISTRY, CELLULAR AND MOLECULAR BIOLOGY PROGRAMT32GM007445 · NIGMS · JOHNS HOPKINS UNIVERSITY · PI GREEN, RACHEL · 1985 to 2021
$24.1M
TRAINING IN AREAS FUNDAMENTAL TO CANCER RESEARCHT32CA009110 · NCI · JOHNS HOPKINS UNIVERSITY · PI MATUNIS, MICHAEL J., WEERARATNA, ASHANI T · 1985 to 2025
$13.1M
NCI NIH HHS T32 CA009110NIGMS NIH HHS T32 GM007445
6 · The paper itself

Abstract

The type I intermediate filament keratin 16 (KRT16 gene; K16 protein) is constitutively expressed in ectoderm-derived appendages and in palmar/plantar epidermis and is robustly induced when the epidermis experiences chemical, mechanical or environmental stress. Missense mutations at the KRT16 locus can cause pachyonychia congenita (PC, OMIM:167200) or focal non-epidermolytic palmoplantar keratoderma (FNEPPK, OMIM:613000), which each entail painful calluses on palmar and plantar skin. Krt16-null mice develop footpad lesions that mimic PC-associated PPK, providing an opportunity to decipher its pathophysiology, and develop therapies. We report on insight gained from a genome-wide analysis of gene expression in PPK-like lesions of Krt16-null mice. Comparison of this data set with publicly available microarray data of PPK lesions from individuals with PC revealed significant synergies in gene expression profiles. Keratin 9 (Krt9/K9), the most robustly expressed gene in differentiating volar keratinocytes, is markedly downregulated in Krt16-null paw skin, well-ahead of lesion onset, and is paralleled by pleiotropic defects in terminal differentiation. Effective prevention of PPK-like lesions in Krt16-null paw skin (via topical delivery of the Nrf2 inducer sulforaphane) involves the stimulation of Krt9 expression. These findings highlight a role for defective terminal differentiation and loss of Krt9/K9 expression as additional drivers of PC-associated PPK and highlight restoration of KRT9 expression as a worthy target for therapy. Further, we report on the novel observation that keratin 16 can localize to the nucleus of epithelial cells, implying a potential nuclear function that may be relevant to PC and FNEPPK.

Indexed as

AnimalsCell DifferentiationDermisHeLa CellsHumansInterleukin-1IsothiocyanatesKelch-Like ECH-Associated Protein 1Keratin-16Keratin-9KeratinocytesKeratinsKeratoderma, PalmoplantarMiceMice, Inbred C57BLMice, KnockoutInterleukin-1IsothiocyanatesKelch-Like ECH-Associated Protein 1Keratin-16Keratin-9KeratinsKRT9 protein, mouseNfe2l2 protein, mouseNF-E2-Related Factor 2sulforaphaneSulfoxides

Identifiers

PMID31220272
PMCPMC6602407
OpenAlexW2923925249

What OpenQuestion holds

Textmetadata
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 OpenQuestion graph.