Inhibiting Protein Kinase Activity of Pyruvate Kinase M2 by SIRT2 Deacetylase Attenuates Psoriasis.

The Journal of Investigative Dermatology
Lihua HaoByung-Hyun Park

Abstract

Signal transducer and activator of transcription 3 (STAT3) is crucial for the pathogenesis of psoriasis. Studies describe pleiotropic roles for a glycolytic enzyme pyruvate kinase M2 (PKM2) as a nuclear kinase of STAT3. However, little is known about the function of PKM2 in T helper type 17 cells in association with STAT3. In this study, we investigated whether and how SIRT2 deacetylase regulated the protein kinase function of PKM2 in T helper type 17 cell‒mediated inflammatory responses in psoriasis. Sirt2 knockout mice and wild-type littermates had psoriatic dermatitis induced by topical treatment of imiquimod or intradermal injection of recombinant IL-23. An initial downregulation of SIRT2 and an increase in PKM2 acetylation and STAT3 phosphorylation were observed in psoriasiform lesions of mice. SIRT2 directly interacted with and deacetylated PKM2 to suppress STAT3 phosphorylation. Consequently, psoriasiform skin inflammation was aggravated in Sirt2 knockout mice. Conversely, genetic re-expression of Sirt2 or pharmacological blockade of PKM2 decreased the disease severity. Flow cytometric analysis of skin tissues of Sirt2 knockout mice showed enhanced infiltration of T helper type 17 cells. Ex vivo experiments showed that S...Continue Reading

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Citations

Apr 14, 2021·Annual Review of Biochemistry·Miao Wang, Hening Lin
Jul 9, 2021·Life Sciences·Shahab Shahgaldi, Fatemeh Rezaei Kahmini
Aug 8, 2021·British Journal of Pharmacology·Lihua HaoByung-Hyun Park

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