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

Thyroid cancer is the most common endocrine malignancy. ¹³¹ 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 ¹³¹ I-induced radiation sialadenitis. Here, we report that LIS1 was reduced by ¹³¹ 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 ¹³¹ 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 ¹³¹ 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 ¹³¹ I ablation therapy may provide a practical and effective way to prevent radiation sialadenitis for DTC patients.
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.
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