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Phenylephrine alleviates 131 I damage in submandibular gland through promoting endogenous stem cell regeneration via lissencephaly-1 upregulation.

Authors :
Wang XY
Yu J
Zhang Y
Zhang FY
Liu KJ
Xiang B
Source :
Toxicology and applied pharmacology [Toxicol Appl Pharmacol] 2020 Jun 01; Vol. 396, pp. 114999. Date of Electronic Publication: 2020 Apr 09.
Publication Year :
2020

Abstract

Thyroid cancer is the most common endocrine malignancy. <superscript>131</superscript> I ablation therapy is an effective treatment for patients with differentiated thyroid cancer (DTC) but frequently causes radiation damage in salivary glands (SGs). Stem cell-based regenerative therapy has been found to reduce radiation sialadenitis. We hypothesize that microtubule motor-regulating protein lissencephaly-1 (LIS1) may be a key stem cell regulator responsible for its efficacy and that upregulating LIS1 would decrease <superscript>131</superscript> I-induced radiation sialadenitis. Here, we report that LIS1 was reduced by <superscript>131</superscript> I in submandibular glands (SMGs) of rats, using both proteomic analysis and Western blot approach. Moreover, the levels of LIS1-Sca-1 and LIS1-SOX2 were downregulated by <superscript>131</superscript> I together with the decrease of LIS1. In contrast, phenylephrine pretreatment enhanced LIS1 and improved the co-expressions and co-localizations of LIS1-Sca-1 and LIS1-SOX2 in <superscript>131</superscript> I-irradiated SMGs. Since Sca-1 and SOX2 are the established stem cell biomarkers in salivary gland, our findings demonstrate that LIS1 may be a potential target for regulating stem cell maintenance in irradiated SGs. Importantly, phenylephrine may have the ability to promote endogenous stem cell regeneration in SMGs via upregulating the LIS1/Sca-1 and LIS1/SOX2 signaling pathways, suggesting that phenylephrine application before <superscript>131</superscript> I ablation therapy may provide a practical and effective way to prevent radiation sialadenitis for DTC patients.<br />Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.<br /> (Copyright © 2020 Elsevier Inc. All rights reserved.)

Details

Language :
English
ISSN :
1096-0333
Volume :
396
Database :
MEDLINE
Journal :
Toxicology and applied pharmacology
Publication Type :
Academic Journal
Accession number :
32278511
Full Text :
https://doi.org/10.1016/j.taap.2020.114999