JOURNAL OF SHANGHAI JIAOTONG UNIVERSITY (MEDICAL SCIENCE) ›› 2021, Vol. 41 ›› Issue (3): 371-375.doi: 10.3969/j.issn.1674-8115.2021.03.015

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Physiological function of cholesterol sulfate and its role in related diseases

Yue-ting JIANG1(), Jia-ying NI1, Shen-rui GUO1, Han LI1, Yu-jia ZHUANG1, Feng WANG1,2()   

  1. 1.Department of Immunology and Microbiology, Shanghai Jiao Tong University College of Basic Medicine Sciences, Shanghai 200025, China
    2.Shanghai Jiao Tong University, Shanghai Institute of Immunology, Shanghai 200025, China
  • Received:2020-02-17 Online:2021-03-28 Published:2021-04-06
  • Contact: Feng WANG;
  • Supported by:
    National Key Research and Development Program of China(SQ2018YFA090045-01);National Natural Science Foundation of China(81771739);Basic Research Project of Shanghai Municipal Commission of Science and Technology(18JC1414100);Innovative Research Team of High-Level Local Universities in Shanghai(SSMU-ZDCX20180101)


Cholesterol sulfate (CS), synthesized by sulfotransferase (SULT) 2B1b, is an important steroid sulfate and plays important physiological roles in the human body. It is widely distributed in human body, such as skin, adrenal gland, liver, lung, brain and endometrium. CS participates in the formation of cornified envelopes and the expression of keratinocyte differentiation markers in the epidermis, thereby regulating epidermal desquamation and barrier function. CS inhibits T cell signaling during thymocyte development in the immune system, and CS/ Cholesterol ratio directly affects thymic selection for T cells, thereby participating in the shaping of T cell receptor repertoire. CS regulates brain metabolism and exerts neuroprotective effects by reducing oxidative stress, maintaining mitochondrial membrane stability and increasing energy reserves. In addition, CS also contributes to the development of many diseases by regulating the activity of functional proteins. The deletion and mutation of steroid sulfatase (STS) gene, which catalyzes the desulfurization of CS, directly leads to the occurrence of X-linked ichthyosis. CS is involved in the development of Alzheimer's disease by promoting the aggregation of amyloid β - protein (Aβ). CS regulates gluconeogenesis by inhibiting the activation of hepatocyte nuclear factor 4α (HNF4α). Thus CS is expected to treat type 2 diabetes. CS has abnormal expression in a variety of cancers, and can interact with matrix metalloproteinase-7 (MMP-7) to induce the aggregation and metastasis of cancer cells. The main challenges and research priorities at this stage are to reveal specific molecular mechanisms under different physiological and pathological conditions and to design feasible clinical treatments.

Key words: cholesterol sulfate (CS), keratinocyte, T cell signaling, glycometabolism, cancer

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