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Gsdma3 is a new factor needed for TNF-α-mediated apoptosis signal pathway in mouse skin keratinocytes

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Abstract

Gsdma3, a newly found gene, is expressed restrictedly in mouse skin keratinocytes and gastrointestinal tract. But until now, there is little information on the regulation and the function of Gsdma3 in skin keratinocytes. In our previous study, we found that Gsdma3 mutation resulted in a decrease in catagen-associated apoptosis of hair follicle keratinocytes. Apoptosis of skin keratinocytes is strictly regulated by a series of signal pathways, among of which, tumor necrosis factor (TNF)-α-induced signal pathway has been extensively studied. To further investigate the role and the pathway of Gsdma3 involved in skin keratinocyte apoptosis, using immunofluorescence, RT-PCR, western blot and TUNEL analysis, we showed here that accompanying TNF-α-induced apoptosis and Caspase-3 expression in mouse skin keratinocytes in vivo and in vitro, Gsdma3 expression was significantly upregulated. After Gsdma3 gene mutation, TNF-α-induced apoptosis and Caspase-3 expression in skin keratinocytes were reduced. The injection of Gsdma3 expression plasmid could directly enhance the apoptosis and Caspase-3 expression in skin keratinocytes. These results, taken together, indicated that in mouse skin keratinocytes, Gsdma3 expression could be regulated by TNF-α. Gsdma3 was not only involved in but also necessary for the TNF-α-induced apoptosis pathway by directly enhancing the Caspase3 expression as well as the apoptosis induction.

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Abbreviations

C57:

C57BL/6

cDNA:

Complimentary DNA

CDS:

Coding sequence

DAB:

Diaminobenzidine

GFP:

Green fluorescent protein

Gsdm :

Gasdermin

HE:

Hematoxylin and eosin

IRS:

Inner root sheath

ISH:

In situ hybridization

ORS:

Outer root sheath

PBS:

Phosphate-buffered saline

PFA:

Paraformaldehyde

RT-PCR:

Reverse transcription polymerase chain reaction

TBS:

Tris-buffered saline

TUNEL:

Terminal dUTP nick end-labeling

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Acknowledgments

This study was supported by grants 30872270 from National Nature Science Foundation of China and CSTC, 2009AA5045 from Key Science and Technology Program of Chongqing.

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Correspondence to Tian Yang or Xiaohua Lian.

Additional information

M. Lei and X. Bai have contributed equally to this work.

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Lei, M., Bai, X., Yang, T. et al. Gsdma3 is a new factor needed for TNF-α-mediated apoptosis signal pathway in mouse skin keratinocytes. Histochem Cell Biol 138, 385–396 (2012). https://doi.org/10.1007/s00418-012-0960-1

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  • DOI: https://doi.org/10.1007/s00418-012-0960-1

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