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The role of PI3K/AKT/FOXO signaling in psoriasis

  • Miao Zhang
  • Xiaoyan ZhangEmail author
Review
  • 125 Downloads

Abstract

Phosphatidylinositol 3-kinase (PI3K) and protein kinase B (AKT) signaling pathway play a central role in multiple cellular functions such as cell proliferation and survival. The forkhead box O (FOXO) transcription factors are negatively regulated by the PI3K/AKT signaling pathway and considered to have inhibitory effect on cell proliferation. Psoriasis is a multifactorial disease with a strong genetic background and characterized by hyperproliferative keratinocyte. PI3K signaling regulates proliferation of keratinocyte by activating AKT and other targets, and by inducing FOXO downregulation. The amplification of PI3K and AKT and the loss of the FOXO are gradually being recognized in psoriatic lesions. The upstream and downstream of PI3K/AKT signaling molecules such as tumor suppressor phosphatase and tensin homolog (PTEN) and mammalian target of Rapamycin (mTOR), respectively, are also frequently altered in psoriasis. In this review, we highlight the recent studies on the roles and mechanisms of PI3K and AKT in regulating hyperproliferation of keratinocyte, and the roles of the downstream targets FOXO in psoriasis. Finally, we summarized that PI3K/AKT/FOXO signaling and its upstream and downstream molecule which could be underlying therapeutic target for psoriasis. This article is part of a special issue entitled: PI3K–AKT–FOXO axis in psoriasis.

Keywords

PI3K AKT FOXO Psoriasis PTEN mTOR Hyperproliferation of keratinocyte Psoriatic lesions Inhibitor 

Abbreviations

PI3K

Phosphatidylinositol-4,5-bisphosphate 3-kinase

AKT/PKB

Protein kinase B

FOXO

Forkhead box O

PTEN

Phosphatase and tensin homolog

mTOR

Mammalian target of Rapamycin complex

PDK1

Phosphoinositide-dependent kinase-1

GFR

Growth factor receptor

PH

Pleckstrin homology

PIP3

Phosphatidylinositol 3–5 triphosphate

AFX

Acute-lymphocytic-leukemia-1 fused gene from chromosome X

FKHR

Forkhead in rhabdomyosarcoma

FKHR-L1

FKHR-like 1

IL-22

Interleukin 22

FasL

Fas ligand

TRAIL

TNF-related apoptosis-inducing ligand

TRADD

TNF receptor type 1 associated death domain

BCL2

B-cell lymphoma 2

BIM

Bcl-2-like protein 11

BAD

Bcl-2-associated death promoter

FLS

Synovial cells

NHEK

Normal human epidermal keratinocyte

IMQ

Imiquimod

ROS

Reactive oxygen species

Notes

Funding

This work was supported by a grant from the National Natural Science Foundation of China (Grant numbers: 81573048).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

This article does not contain any studies with human participants or animals performed by any of the authors.

Informed consent

This article does not contain any studies with human participants or animals performed by any of the authors; therefore, informed consent is not applicable.

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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Graduate SchoolBeijing University of Chinese MedicineBeijingChina
  2. 2.Department of DermatologyChina-Japan Friendship HospitalBeijingChina

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