Gene Loss

Publication Details

Identifier: JB_XDZIDN

Curator: Gonçalo Themudo

DOI: 10.1038/s41598-017-17782-4

PMID: 29234126

Title:

Epidermal cornification is preceded by the expression of a keratinocyte-specific set of pyroptosis-related genes.

Abstract:

The homeostasis of the epidermis depends on keratinocyte differentiation and cornification, a mode of programmed cell death that does not elicit inflammation. Here, we report that cornification is associated with the expression of specific genes that control multiple steps of pyroptosis, another form of cell death that involves the processing and release of interleukin-1 family (IL1F) cytokines. Expression levels of pro-inflammatory IL1A and IL1B and of the pyroptotic pore-forming gasdermin (GSDM) D were downregulated during terminal differentiation of human keratinocytes in vitro. By contrast, negative regulators of IL-1 processing, including NLR family pyrin domain containing 10 (NLRP10) and pyrin domain-containing 1 (PYDC1), the anti-inflammatory IL1F members IL-37 (IL1F7) and IL-38 (IL1F10), and GSDMA, were strongly induced in differentiated keratinocytes. In human tissues, these keratinocyte differentiation-associated genes are expressed in the skin at higher levels than in any other organ, and mammalian species, that have lost the epidermal cornification program during evolution, i.e. whales and dolphins, lack homologs of these genes. Together, our results suggest that human epidermal cornification is accompanied by a tight control of pyroptosis and warrant further studies of potential defects in the balance between cornification and pyroptosis in skin pathologies.

Last update:

24-03-2025

Associated Glosses (62 results)

GlossID	Species	Symbol	Gene Loss Mechanism	Loss Type	Lineage Specific	Citation
GL_E8A4NQ	Orcinus orca	GSDMC	LOF (frameshift, premature stop, ss)	Full	No	10.1038/s41598-017-17782-4
GL_ETEWVD	Physeter catodon	NLRP10	Other	Full	No	10.1038/s41598-017-17782-4
GL_FQCXA4	Orcinus orca	NLRP1	Other	Full	No	10.1038/s41598-017-17782-4
GL_FTKZFV	Balaenoptera acutorostrata	NLRP10	Other	Full	No	10.1038/s41598-017-17782-4
GL_GQEI4E	Physeter catodon	GSDMC	LOF (frameshift, premature stop, ss)	Full	No	10.1038/s41598-017-17782-4
GL_GUDGYF	Orcinus orca	IL36A	Gene deletion	Full	Cetacea	10.1038/s41598-017-17782-4
GL_H4TO3R	Balaenoptera acutorostrata	IL1F10	LOF (frameshift, premature stop, ss)	Full	Cetacea	10.1038/s41598-017-17782-4
GL_HVX4BI	Lipotes vexillifer	IL36A	Gene deletion	Full	Cetacea	10.1038/s41598-017-17782-4
GL_I3QCMU	Lipotes vexillifer	IL1F10	LOF (frameshift, premature stop, ss)	Full	Cetacea	10.1038/s41598-017-17782-4
GL_JIWWKU	Orcinus orca	CASP14	Other	Full	Cetacea	10.1038/s41598-017-17782-4