4.6 Review

Progranulin as a Potential Therapeutic Target in Immune-Mediated Diseases

Journal

JOURNAL OF INFLAMMATION RESEARCH
Volume 14, Issue -, Pages 6543-6556

Publisher

DOVE MEDICAL PRESS LTD
DOI: 10.2147/JIR.S339254

Keywords

PGRN; TNF-alpha; TNFR; immune-mediated diseases; therapeutic

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Funding

  1. National Natural Science Foundation of China [81274172, 81473267, 81973637]
  2. National Traditional Chinese Medicine Inheritance and Innovation Hundreds and Thousands Talent Project: Young Qihuang Scholar Support Project of the State Administration of Traditional Chinese Medicine in 2020

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Progranulin, a secretory glycoprotein, plays a protective role in the development of various immune-mediated diseases by regulating critical signaling pathways. Its immunological functions and role in disease pathogenesis, despite controversy in some diseases, provide new ideas for therapeutic strategies.
Progranulin (PGRN), a secretory glycoprotein consisting of 593 amino acid residues, is a key actor and regulator of multiple system functions such as innate immune response and inflammation, as well as tissue regeneration. Recently, there is emerging evidence that PGRN is protective in the development of a variety of immune-mediated diseases, including rheumatoid arthritis (RA), inflammatory bowel disease (IBD), type 1 diabetes mellitus (T1DM) and multiple sclerosis (MS) by regulating signaling pathways known to be critical for immunology, particularly the tumor necrosis factor alpha/TNF receptor (TNF-alpha/TNFR) signaling pathway. Whereas, the role of PGRN in psoriasis, systemic lupus erythematosus (SLE) and systemic sclerosis (SSc) is controversial. This review summarizes the immunological functions of PGRN and its role in the pathogenesis of several immune-mediated diseases, in order to provide new ideas for developing therapeutic strategies for these diseases.

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