Physiological function of nerve injury-induced protein 1 and its role in relevant diseases

doi:10.3969/j.issn.1674-8115.2023.03.012

Abstract

Abstract:

Nerve injury-induced protein 1 (NINJ1) is a cell-surface adhesion molecule containing an extracellular adhesion domain and two transmembrane domains. NINJ1 is named for its original discovery in damaged nerve endings. It is expressed in a variety of tissues and cells, with high expression in epithelial and myeloid cells. NINJ1 regulates nerve regeneration by promoting Schwann cell precursors and pluripotent pericytes to differentiate into Schwann cells. In diabetes-induced peripheral nerve and vascular damage, NINJ1 not only promotes nerve repair, but also regulates penile angiogenesis via angiopoietin 1 (ANG1)/tyrosine-protein kinase receptor tie-2 (TIE2) signaling pathway. NINJ1 also participates in the maturation of vitreous vascular network, which is associated with changes in the proportion of ANG1 and ANG2 in pericytes. NINJ1 mediates inflammatory cell migration across the endothelium through its extracellular adhesion domain, and thus aggravates central nervous system inflammation. However, NINJ1 cleaved by matrix metalloproteinase 9 (MMP9) can inhibit macrophage inflammatory activation, and its mimic peptide is expected to treat atherosclerosis. In addition to regulating the inflammatory phenotypes of myeloid cells, NINJ1 actively mediates plasma membrane rupture and regulates programmed cell death, which is involved in host defense against exogenous infection. Moreover, NINJ1 is up-regulated in a variety of tumor tissues, and regulates tumor suppressor P53 activity via the P53-NINJ1 loop, which mediates tumor growth and metastasis. The current review summarizes the physiological function of NINJ1 and its key regulatory roles in pathological processes, and discusses its potential value in immunomodulation and tissue regeneration, in order to provide new ideas for the prevention and treatment of injury, inflammation and tumor-related diseases.

Key words: nerve injury-induced protein 1 (NINJ1), nerve injury, tumor, angiogenesis, inflammation

CLC Number:

WU Zhaoyu, XU Zhijue, PU Hongji, WANG Xin, LU Xinwu. Physiological function of nerve injury-induced protein 1 and its role in relevant diseases[J]. Journal of Shanghai Jiao Tong University (Medical Science), 2023, 43(3): 358-364.

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References 46

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