Lysine Demethylase 1B Promotes Tear Secretion Disorder in Sjogren’s Syndrome by Regulating the PAX6/CLU Axis

Liu, Shuang; Tang, Shaohua; Yang, Guang; Li, Qingnan

doi:10.1007/s12031-022-02094-8

Cited by 1 publication

(4 citation statements)

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“…PAX6 knockout in human corneal epithelial cells recently revealed its role in the regulation of CLU gene expression [126]. Indeed, a PAX6-dependent increase in CLU gene expression was observed in mice lacrimal glands [127].…”

Section: Pax6mentioning

confidence: 99%

“…It is a multifactorial disease characterized by the loss of tear film homeostasis caused by its instability and hyperosmolarity, as well as inflammation and damage to the ocular surface and neurosensory abnormalities leading to symptoms like foreign body sensation or burning sensation [257]. Interestingly, low levels of CLU expression have been observed in the tear film of human DED patients and in Sjogren's syndrome mice [127,232]. The interference of the epithelial turnover cycle results in the loss of apical cells and barrier disruption.…”

Section: Dmmentioning

confidence: 99%

“…In Sjögren syndrome, epigenetic markers are altered and closely linked to progression of the disease [262]. In particular, histone demethylation (H3K4me2) increases PAX6 expression, leading to increased CLU expression in lacrimal glands and reversing disorders by improved tear film secretion [127]. Matrix metalloproteinase (MMP) activity, especially that of MMP9, has been linked with DED in several studies [263][264][265][266]; interestingly, CLU was found to be an inhibitor of MMP9, regulating its activity and therefore posing as a potential therapeutic target for DED [232,267].…”

Section: Dmmentioning

confidence: 99%

“…Low level of CLU in tear film leading to loss of apical cells and barrier disuruption [127,232] • CLU improve tear film secretion [127] and seal deficits in the epithelial barrier [233,234] Anterior chamber (aquous humor) Yes AMD • CLU enrichment [235] Table 1. Cont.…”

mentioning

confidence: 99%

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The Ins and Outs of Clusterin: Its Role in Cancer, Eye Diseases and Wound Healing

Gross,

Guérin,

Socol

et al. 2023

IJMS

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Clusterin (CLU) is a glycoprotein originally discovered in 1983 in ram testis fluid. Rapidly observed in other tissues, it was initially given various names based on its function in different tissues. In 1992, it was finally named CLU by consensus. Nearly omnipresent in human tissues, CLU is strongly expressed at fluid–tissue interfaces, including in the eye and in particular the cornea. Recent research has identified different forms of CLU, with the most prominent being a 75–80 kDa heterodimeric protein that is secreted. Another truncated version of CLU (55 kDa) is localized to the nucleus and exerts pro-apoptotic activities. CLU has been reported to be involved in various physiological processes such as sperm maturation, lipid transportation, complement inhibition and chaperone activity. CLU was also reported to exert important functions in tissue remodeling, cell–cell adhesion, cell–substratum interaction, cytoprotection, apoptotic cell death, cell proliferation and migration. Hence, this protein is sparking interest in tissue wound healing. Moreover, CLU gene expression is finely regulated by cytokines, growth factors and stress-inducing agents, leading to abnormally elevated levels of CLU in many states of cellular disturbance, including cancer and neurodegenerative conditions. In the eye, CLU expression has been reported as being severely increased in several pathologies, such as age-related macular degeneration and Fuch’s corneal dystrophy, while it is depleted in others, such as pathologic keratinization. Nevertheless, the precise role of CLU in the development of ocular pathologies has yet to be deciphered. The question of whether CLU expression is influenced by these disorders or contributes to them remains open. In this article, we review the actual knowledge about CLU at both the protein and gene expression level in wound healing, and explore the possibility that CLU is a key factor in cancer and eye diseases. Understanding the expression and regulation of CLU could lead to the development of novel therapeutics for promoting wound healing.

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Section: Pax6mentioning

confidence: 99%