High Glucose Reduces the Paracellular Permeability of the Submandibular Gland Epithelium via the MiR-22-3p/Sp1/Claudin Pathway

Tight junctions (TJs) play an important role in water, ion, and solute transport through the paracellular pathway of epithelial cells; however, their role in diabetes-induced salivary gland dysfunction remains unknown. Here, we found that the TJ proteins claudin-1 and claudin-3 were significantly in...

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Autores principales:	Yan Huang, Hui-Min Liu, Qian-Ying Mao, Xin Cong, Yan Zhang, Sang-Woo Lee, Kyungpyo Park, Li-Ling Wu, Ruo-Lan Xiang, Guang-Yan Yu
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	diabetes submandibular gland microRNA-22-3p tight junction specificity protein-1 Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/9551a39fed334b61b08c6df8a8810a73
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spelling	oai:doaj.org-article:9551a39fed334b61b08c6df8a8810a732021-11-25T17:13:06ZHigh Glucose Reduces the Paracellular Permeability of the Submandibular Gland Epithelium via the MiR-22-3p/Sp1/Claudin Pathway10.3390/cells101132302073-4409https://doaj.org/article/9551a39fed334b61b08c6df8a8810a732021-11-01T00:00:00Zhttps://www.mdpi.com/2073-4409/10/11/3230https://doaj.org/toc/2073-4409Tight junctions (TJs) play an important role in water, ion, and solute transport through the paracellular pathway of epithelial cells; however, their role in diabetes-induced salivary gland dysfunction remains unknown. Here, we found that the TJ proteins claudin-1 and claudin-3 were significantly increased in the submandibular glands (SMGs) of db/db mice and high glucose (HG)-treated human SMGs. HG decreased paracellular permeability and increased claudin-1 and claudin-3 expression in SMG-C6 cells. Knockdown of claudin-1 or claudin-3 reversed the HG-induced decrease in paracellular permeability. MiR-22-3p was significantly downregulated in diabetic SMGs and HG-treated SMG-C6 cells. A miR-22-3p mimic suppressed claudin-1 and claudin-3 expression and abolished the HG-induced increases in claudin-1 and claudin-3 levels in SMG-C6 cells, whereas a miR-22-3p inhibitor produced the opposite effects. Specificity protein-1 (Sp1) was enhanced in diabetic SMGs and HG-treated SMG-C6 cells, which promoted claudin-1 and claudin-3 transcription through binding to the corresponding promoters. A luciferase reporter assay confirmed that miR-22-3p repressed Sp1 by directly targeting the Sp1 mRNA 3′-untranslated region (3′-UTR). Consistently, the miR-22-3p mimic suppressed, whereas the miR-22-3p inhibitor enhanced, the effects of HG on Sp1 expression. Taken together, our results demonstrate a new regulatory pathway through which HG decreases the paracellular permeability of SMG cells by inhibiting miR-22-3p/Sp1-mediated claudin-1 and claudin-3 expression.Yan HuangHui-Min LiuQian-Ying MaoXin CongYan ZhangSang-Woo LeeKyungpyo ParkLi-Ling WuRuo-Lan XiangGuang-Yan YuMDPI AGarticlediabetessubmandibular glandmicroRNA-22-3ptight junctionspecificity protein-1Biology (General)QH301-705.5ENCells, Vol 10, Iss 3230, p 3230 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	diabetes submandibular gland microRNA-22-3p tight junction specificity protein-1 Biology (General) QH301-705.5
spellingShingle	diabetes submandibular gland microRNA-22-3p tight junction specificity protein-1 Biology (General) QH301-705.5 Yan Huang Hui-Min Liu Qian-Ying Mao Xin Cong Yan Zhang Sang-Woo Lee Kyungpyo Park Li-Ling Wu Ruo-Lan Xiang Guang-Yan Yu High Glucose Reduces the Paracellular Permeability of the Submandibular Gland Epithelium via the MiR-22-3p/Sp1/Claudin Pathway
description	Tight junctions (TJs) play an important role in water, ion, and solute transport through the paracellular pathway of epithelial cells; however, their role in diabetes-induced salivary gland dysfunction remains unknown. Here, we found that the TJ proteins claudin-1 and claudin-3 were significantly increased in the submandibular glands (SMGs) of db/db mice and high glucose (HG)-treated human SMGs. HG decreased paracellular permeability and increased claudin-1 and claudin-3 expression in SMG-C6 cells. Knockdown of claudin-1 or claudin-3 reversed the HG-induced decrease in paracellular permeability. MiR-22-3p was significantly downregulated in diabetic SMGs and HG-treated SMG-C6 cells. A miR-22-3p mimic suppressed claudin-1 and claudin-3 expression and abolished the HG-induced increases in claudin-1 and claudin-3 levels in SMG-C6 cells, whereas a miR-22-3p inhibitor produced the opposite effects. Specificity protein-1 (Sp1) was enhanced in diabetic SMGs and HG-treated SMG-C6 cells, which promoted claudin-1 and claudin-3 transcription through binding to the corresponding promoters. A luciferase reporter assay confirmed that miR-22-3p repressed Sp1 by directly targeting the Sp1 mRNA 3′-untranslated region (3′-UTR). Consistently, the miR-22-3p mimic suppressed, whereas the miR-22-3p inhibitor enhanced, the effects of HG on Sp1 expression. Taken together, our results demonstrate a new regulatory pathway through which HG decreases the paracellular permeability of SMG cells by inhibiting miR-22-3p/Sp1-mediated claudin-1 and claudin-3 expression.
format	article
author	Yan Huang Hui-Min Liu Qian-Ying Mao Xin Cong Yan Zhang Sang-Woo Lee Kyungpyo Park Li-Ling Wu Ruo-Lan Xiang Guang-Yan Yu
author_facet	Yan Huang Hui-Min Liu Qian-Ying Mao Xin Cong Yan Zhang Sang-Woo Lee Kyungpyo Park Li-Ling Wu Ruo-Lan Xiang Guang-Yan Yu
author_sort	Yan Huang
title	High Glucose Reduces the Paracellular Permeability of the Submandibular Gland Epithelium via the MiR-22-3p/Sp1/Claudin Pathway
title_short	High Glucose Reduces the Paracellular Permeability of the Submandibular Gland Epithelium via the MiR-22-3p/Sp1/Claudin Pathway
title_full	High Glucose Reduces the Paracellular Permeability of the Submandibular Gland Epithelium via the MiR-22-3p/Sp1/Claudin Pathway
title_fullStr	High Glucose Reduces the Paracellular Permeability of the Submandibular Gland Epithelium via the MiR-22-3p/Sp1/Claudin Pathway
title_full_unstemmed	High Glucose Reduces the Paracellular Permeability of the Submandibular Gland Epithelium via the MiR-22-3p/Sp1/Claudin Pathway
title_sort	high glucose reduces the paracellular permeability of the submandibular gland epithelium via the mir-22-3p/sp1/claudin pathway
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/9551a39fed334b61b08c6df8a8810a73
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High Glucose Reduces the Paracellular Permeability of the Submandibular Gland Epithelium via the MiR-22-3p/Sp1/Claudin Pathway

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