Cargando…
Pyruvate Kinase M2 Mediates Glycolysis Contributes to Psoriasis by Promoting Keratinocyte Proliferation
Psoriasis is characterized by keratinocyte proliferation and immune cell infiltration. M2 isoform of pyruvate kinase (PKM2) was reported to have an important role in cell proliferation, which is a rate-limiting enzyme that regulates the final step of glycolysis. However, how PKM2 regulates cell meta...
Autores principales: | , , , , , , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2021
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8558409/ https://www.ncbi.nlm.nih.gov/pubmed/34733164 http://dx.doi.org/10.3389/fphar.2021.765790 |
_version_ | 1784592554381017088 |
---|---|
author | Liu, Yun-zi Xu, Ming-yuan Dai, Xiao-yu Yan, Lang Li, Lei Zhu, Rui-zhen Ren, Li-jun Zhang, Ji-qian-zhu Zhang, Xiao-fang Li, Jin-feng Tian, Yi-jun Shi, Wen-jing Liu, Ye-qiang Jiang, Chun-lei Zhu, Jiang-bo Chen, Ji-kuai |
author_facet | Liu, Yun-zi Xu, Ming-yuan Dai, Xiao-yu Yan, Lang Li, Lei Zhu, Rui-zhen Ren, Li-jun Zhang, Ji-qian-zhu Zhang, Xiao-fang Li, Jin-feng Tian, Yi-jun Shi, Wen-jing Liu, Ye-qiang Jiang, Chun-lei Zhu, Jiang-bo Chen, Ji-kuai |
author_sort | Liu, Yun-zi |
collection | PubMed |
description | Psoriasis is characterized by keratinocyte proliferation and immune cell infiltration. M2 isoform of pyruvate kinase (PKM2) was reported to have an important role in cell proliferation, which is a rate-limiting enzyme that regulates the final step of glycolysis. However, how PKM2 regulates cell metabolism and proliferation in psoriatic keratinocytes is still poorly understood. Interestingly, we found that PKM2 was highly expressed in psoriatic epidermis from patients and mouse models. PKM2 overexpression promoted keratinocyte glycolytic metabolism while knockdown inhibited keratinocyte proliferation and glycolysis. Mice lacking PKM2 specifically in keratinocytes, pharmacological inhibition of PKM2 or glycolysis inhibited keratinocyte proliferation and showed obvious remission in an imiquimod-induced psoriatic mouse model. Moreover, the inhibitor of the EGF-receptor blocked EGF-stimulated PKM2 expression and glycolysis in keratinocytes. We identify PKM2 as an upregulated gene in psoriasis. PKM2 is essential in keratinocyte over-proliferation and may represent a therapeutic target for psoriasis. |
format | Online Article Text |
id | pubmed-8558409 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-85584092021-11-02 Pyruvate Kinase M2 Mediates Glycolysis Contributes to Psoriasis by Promoting Keratinocyte Proliferation Liu, Yun-zi Xu, Ming-yuan Dai, Xiao-yu Yan, Lang Li, Lei Zhu, Rui-zhen Ren, Li-jun Zhang, Ji-qian-zhu Zhang, Xiao-fang Li, Jin-feng Tian, Yi-jun Shi, Wen-jing Liu, Ye-qiang Jiang, Chun-lei Zhu, Jiang-bo Chen, Ji-kuai Front Pharmacol Pharmacology Psoriasis is characterized by keratinocyte proliferation and immune cell infiltration. M2 isoform of pyruvate kinase (PKM2) was reported to have an important role in cell proliferation, which is a rate-limiting enzyme that regulates the final step of glycolysis. However, how PKM2 regulates cell metabolism and proliferation in psoriatic keratinocytes is still poorly understood. Interestingly, we found that PKM2 was highly expressed in psoriatic epidermis from patients and mouse models. PKM2 overexpression promoted keratinocyte glycolytic metabolism while knockdown inhibited keratinocyte proliferation and glycolysis. Mice lacking PKM2 specifically in keratinocytes, pharmacological inhibition of PKM2 or glycolysis inhibited keratinocyte proliferation and showed obvious remission in an imiquimod-induced psoriatic mouse model. Moreover, the inhibitor of the EGF-receptor blocked EGF-stimulated PKM2 expression and glycolysis in keratinocytes. We identify PKM2 as an upregulated gene in psoriasis. PKM2 is essential in keratinocyte over-proliferation and may represent a therapeutic target for psoriasis. Frontiers Media S.A. 2021-10-18 /pmc/articles/PMC8558409/ /pubmed/34733164 http://dx.doi.org/10.3389/fphar.2021.765790 Text en Copyright © 2021 Liu, Xu, Dai, Yan, Li, Zhu, Ren, Zhang, Zhang, Li, Tian, Shi, Liu, Jiang, Zhu and Chen. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Pharmacology Liu, Yun-zi Xu, Ming-yuan Dai, Xiao-yu Yan, Lang Li, Lei Zhu, Rui-zhen Ren, Li-jun Zhang, Ji-qian-zhu Zhang, Xiao-fang Li, Jin-feng Tian, Yi-jun Shi, Wen-jing Liu, Ye-qiang Jiang, Chun-lei Zhu, Jiang-bo Chen, Ji-kuai Pyruvate Kinase M2 Mediates Glycolysis Contributes to Psoriasis by Promoting Keratinocyte Proliferation |
title | Pyruvate Kinase M2 Mediates Glycolysis Contributes to Psoriasis by Promoting Keratinocyte Proliferation |
title_full | Pyruvate Kinase M2 Mediates Glycolysis Contributes to Psoriasis by Promoting Keratinocyte Proliferation |
title_fullStr | Pyruvate Kinase M2 Mediates Glycolysis Contributes to Psoriasis by Promoting Keratinocyte Proliferation |
title_full_unstemmed | Pyruvate Kinase M2 Mediates Glycolysis Contributes to Psoriasis by Promoting Keratinocyte Proliferation |
title_short | Pyruvate Kinase M2 Mediates Glycolysis Contributes to Psoriasis by Promoting Keratinocyte Proliferation |
title_sort | pyruvate kinase m2 mediates glycolysis contributes to psoriasis by promoting keratinocyte proliferation |
topic | Pharmacology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8558409/ https://www.ncbi.nlm.nih.gov/pubmed/34733164 http://dx.doi.org/10.3389/fphar.2021.765790 |
work_keys_str_mv | AT liuyunzi pyruvatekinasem2mediatesglycolysiscontributestopsoriasisbypromotingkeratinocyteproliferation AT xumingyuan pyruvatekinasem2mediatesglycolysiscontributestopsoriasisbypromotingkeratinocyteproliferation AT daixiaoyu pyruvatekinasem2mediatesglycolysiscontributestopsoriasisbypromotingkeratinocyteproliferation AT yanlang pyruvatekinasem2mediatesglycolysiscontributestopsoriasisbypromotingkeratinocyteproliferation AT lilei pyruvatekinasem2mediatesglycolysiscontributestopsoriasisbypromotingkeratinocyteproliferation AT zhuruizhen pyruvatekinasem2mediatesglycolysiscontributestopsoriasisbypromotingkeratinocyteproliferation AT renlijun pyruvatekinasem2mediatesglycolysiscontributestopsoriasisbypromotingkeratinocyteproliferation AT zhangjiqianzhu pyruvatekinasem2mediatesglycolysiscontributestopsoriasisbypromotingkeratinocyteproliferation AT zhangxiaofang pyruvatekinasem2mediatesglycolysiscontributestopsoriasisbypromotingkeratinocyteproliferation AT lijinfeng pyruvatekinasem2mediatesglycolysiscontributestopsoriasisbypromotingkeratinocyteproliferation AT tianyijun pyruvatekinasem2mediatesglycolysiscontributestopsoriasisbypromotingkeratinocyteproliferation AT shiwenjing pyruvatekinasem2mediatesglycolysiscontributestopsoriasisbypromotingkeratinocyteproliferation AT liuyeqiang pyruvatekinasem2mediatesglycolysiscontributestopsoriasisbypromotingkeratinocyteproliferation AT jiangchunlei pyruvatekinasem2mediatesglycolysiscontributestopsoriasisbypromotingkeratinocyteproliferation AT zhujiangbo pyruvatekinasem2mediatesglycolysiscontributestopsoriasisbypromotingkeratinocyteproliferation AT chenjikuai pyruvatekinasem2mediatesglycolysiscontributestopsoriasisbypromotingkeratinocyteproliferation |