Abstract:
:Hyaluronan (HA), the major extracellular matrix component, is often anchored to CD44, a family of structurally/functionally important cell surface receptors. Recent results indicate that UV irradiation (UVR)-induced cutaneous squamous cell carcinomas (SCC) overexpress a variety of CD44 variant isoforms (CD44v), with different CD44v isoforms appear to confer malignant SCC properties. UVR also stimulates HA degradation in epidermal keratinocytes. Both large HA polymers and their UVR-induced catabolic products (small HA) selectively activate CD44-mediated cellular signaling in normal keratinocytes and SCC cells, with all of the downstream processes being mediated by RhoGTPases (e.g., Rac1 and Rho). Importantly, we found that the hormonally active form of vitamin D 1,25(OH)2D3 not only prevents the UVR-induced small HA activation of abnormal keratinocyte behavior and SCC progression, but also enhances large HA stimulation of normal keratinocyte activities and epidermal function(s). The aim of this hypothesis and theory article is to question whether matrix HA and its UVR-induced catabolic products (e.g., large and small HA) can selectively activate CD44-mediated cellular signaling such as GTPase (Rac and RhA) activation. We suggested that large HA-CD44 interaction promotes Rac-signaling and normal keratinocyte differentiation (lipid synthesis), DNA repair, and keratinocyte survival function. Conversely, small HA-CD44 interaction stimulates RhoA activation, NFκB/Stat-3 signaling, and miR-21 production, resulting in inflammation and proliferation as well as SCC progression. We also question whether vitamin D treatment displays any effect on small HA-CD44v-mediated RhoA signaling, inflammation, and SCC progression, as well as large HA-CD44-mediated differentiation, DNA repair, keratinocyte survival, and normal keratinocyte function. In addition, we discussed that the topical application of signaling perturbation agents (e.g., Y27623, a ROK inhibitor) may be used to treat certain skin diseases displaying upregulation of keratinocyte proliferation such as psoriasis and actinic keratoses in order to correct the imbalance between Rac and RhoA signaling during various UV irradiation-induced skin diseases in patients. Finally, we proposed that matrix HA/CD44-signaling strategies and matrix HA (HAS vs. HAL or HAS → HAL)-based therapeutic approaches (together with vitamin D) may be used for the treatment of patients suffering a number of UV irradiation-induced skin diseases (e.g., inflammation, skin cancer, and chronic non-healing wounds).
journal_name
Front Immunoljournal_title
Frontiers in immunologyauthors
Bourguignon LY,Bikle Ddoi
10.3389/fimmu.2015.00224subject
Has Abstractpub_date
2015-05-13 00:00:00pages
224issn
1664-3224journal_volume
6pub_type
杂志文章,评审abstract::A transplanted organ is usually rejected without any major immunosuppressive treatment because of vigorous alloimmune responsiveness. However, continuous global immunosuppression may cause severe side effects, including nephrotoxicity, tumors, and infections. Therefore, it is necessary to seek novel immunosuppressive ...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2019.00652
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journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2020.00744
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journal_title:Frontiers in immunology
pub_type: 杂志文章
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journal_title:Frontiers in immunology
pub_type: 杂志文章,评审
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pub_type: 杂志文章
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pub_type: 杂志文章
doi:10.3389/fimmu.2019.03068
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abstract::Genetic modification of mesenchymal stem cells (MSCs) is a promising strategy to improve their therapeutic effects. Granulocyte-colony stimulating factor (G-CSF) is a growth factor widely used in the clinical practice with known regenerative and immunomodulatory actions, including the mobilization of regulatory T cell...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2018.01449
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journal_title:Frontiers in immunology
pub_type: 杂志文章,评审
doi:10.3389/fimmu.2017.00586
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journal_title:Frontiers in immunology
pub_type: 杂志文章
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journal_title:Frontiers in immunology
pub_type: 杂志文章,评审
doi:10.3389/fimmu.2019.02806
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journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2018.01350
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journal_title:Frontiers in immunology
pub_type: 杂志文章,评审
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journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2019.02985
更新日期:2020-01-09 00:00:00
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journal_title:Frontiers in immunology
pub_type: 杂志文章,评审
doi:10.3389/fimmu.2019.00596
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journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2017.00821
更新日期:2017-07-19 00:00:00
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journal_title:Frontiers in immunology
pub_type: 杂志文章,评审
doi:10.3389/fimmu.2018.02929
更新日期:2018-12-12 00:00:00
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journal_title:Frontiers in immunology
pub_type: 杂志文章,评审
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pub_type: 杂志文章
doi:10.3389/fimmu.2018.00619
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journal_title:Frontiers in immunology
pub_type: 杂志文章
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journal_title:Frontiers in immunology
pub_type: 杂志文章,评审
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journal_title:Frontiers in immunology
pub_type: 杂志文章,评审
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journal_title:Frontiers in immunology
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pub_type: 杂志文章,评审
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journal_title:Frontiers in immunology
pub_type: 杂志文章
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