The emerging role of PKM in keratinocyte homeostasis and pathophysiology

Increased aerobic glycolysis in keratinocytes has been reported as a hallmark of skin diseases while its pharmacological inhibition restores keratinocyte homeostasis. Pyruvate kinase muscle (PKM) isoforms are key enzymes in the glycolytic pathway and, therefore, an attractive therapeutic target. Sim...

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Bibliographic Details
Published in:The FEBS journal 2023-05, Vol.290 (9), p.2311-2319
Main Authors: Demeter, Jenna B., Elshaarrawi, Ahmed, Dowker‐Key, Presley D., Bettaieb, Ahmed
Format: Article
Language:English
Subjects:
CRISPR
CRISPR/Cas9 system
gene editing
Gene expression
Genetic modification
Glycolysis
Glycolysis - genetics
Homeostasis
Humans
inflammation
Isoforms
Keratinocytes
Metabolism
Molecular modelling
Muscles - metabolism
Pathophysiology
Perturbation
PKM1
PKM2
proliferation
Protein Isoforms - metabolism
psoriasis
Pyruvate kinase
Pyruvate Kinase - genetics
Pyruvate Kinase - metabolism
Pyruvic acid
RNA Splicing
Skin diseases
Therapeutic applications
Therapeutic targets
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Summary:Increased aerobic glycolysis in keratinocytes has been reported as a hallmark of skin diseases while its pharmacological inhibition restores keratinocyte homeostasis. Pyruvate kinase muscle (PKM) isoforms are key enzymes in the glycolytic pathway and, therefore, an attractive therapeutic target. Simon Nold and colleagues used CRISPR/Cas9‐mediated gene editing to investigate the outcomes of PKM splicing perturbations and specific PKM1 or PKM2 deficiency in human HaCaT keratinocytes. Collectively, the study demonstrated different effects of PKM1 or PKM2 depletion on the reciprocal PKM isoform and on keratinocyte gene expression, metabolism and proliferation. Findings from this study provide novel insights into the role of PKM in keratinocyte homeostasis, warranting additional investigations into the underlying molecular mechanisms and potential therapeutic applications. Pyruvate kinase muscle (PKM) isoforms are key glycolytic pathway enzymes and, therefore, attractive therapeutic targets. Simon Nold and colleagues investigated the effect of PKM splicing perturbations and PKM1 or PKM2 deficiency on human HaCaT keratinocytes. They demonstrated different effects of PKM1 or PKM2 depletion on the reciprocal PKM isoform and on keratinocyte gene expression, metabolism and proliferation. These results highlight the role of PKM in keratinocyte homeostasis, warranting additional investigations into the underlying molecular mechanisms and potential therapeutic applications. Comment on: https://doi.org/10.1111/febs.16625
ISSN:1742-464X
1742-4658
DOI:10.1111/febs.16700