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衰老大鼠固有层中钙通道增加。

Increased calcium channel in the lamina propria of aging rat.

作者信息

Kim Ji Min, Heo Hyoung-Sam, Shin Sung-Chan, Kwon Hyun-Keun, Lee Jin-Choon, Sung Eui-Suk, Kim Hyung-Sik, Park Gi Cheol, Lee Byung-Joo

机构信息

Biomedical Research Institute, Pusan National University Hospital, Busan, Republic of Korea.

Division of Bio-Medical Informatics, Center for Genome Science, Korea National Institute of Health, Korea Centers for Disease Control and Prevention, Cheongju-si, Republic of Korea.

出版信息

Aging (Albany NY). 2019 Oct 31;11(20):8810-8824. doi: 10.18632/aging.102284.

DOI:10.18632/aging.102284
PMID:31682233
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6834399/
Abstract

The alterations of the extracellular matrix (ECM) in lamina propria of the vocal folds are important changes that are associated with decreased vibrations and increased stiffness in aging vocal fold. The aim of this study was to investigate the differences in gene expression of lamina propria using next generation sequencing (NGS) in young and aging rats and to identify genes that affect aging-related ECM changes for developing novel therapeutic target molecule. Among the 40 genes suggested in the NGS analysis, voltage-gated calcium channels (VGCC) subunit alpha1 S (CACNA1S), VGCC auxiliary subunit beta 1 (CACNB1), and VGCC auxiliary subunit gamma 1 (CACNG1) were increased in the lamina propria of the old rats compared to the young rats. The synthesis of collagen I and III in hVFFs decreased after si-CACNA1S and verapamil treatment. The expression and activity of matrix metalloproteinases (MMP)-1 and -8 were increased in hVFFs after the treatment of verapamil. However, there was no change in the expression of MMP-2 and -9. These results suggest that some calcium channels may be related with the alteration of aging-related ECM in vocal folds. Calcium channel has promising potential as a novel therapeutic target for the remodeling ECM of aging lamina propria.

摘要

声带固有层细胞外基质（ECM）的改变是重要变化，与衰老声带振动减少和硬度增加有关。本研究的目的是使用下一代测序（NGS）研究年轻和衰老大鼠声带固有层基因表达的差异，并确定影响衰老相关ECM变化的基因，以开发新的治疗靶点分子。在NGS分析中提出的40个基因中，与年轻大鼠相比，老年大鼠声带固有层中电压门控钙通道（VGCC）亚基α1 S（CACNA1S）、VGCC辅助亚基β1（CACNB1）和VGCC辅助亚基γ1（CACNG1）增加。si-CACNA1S和维拉帕米处理后，人声带成纤维细胞（hVFFs）中I型和III型胶原蛋白的合成减少。维拉帕米处理后，hVFFs中基质金属蛋白酶（MMP）-1和-8的表达及活性增加。然而，MMP-2和-9的表达没有变化。这些结果表明，一些钙通道可能与声带衰老相关ECM的改变有关。钙通道作为衰老固有层ECM重塑的新型治疗靶点具有广阔前景。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f0df/6834399/8676e9b21579/aging-11-102284-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f0df/6834399/9f050d5cad50/aging-11-102284-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f0df/6834399/67c2cf0b9dd9/aging-11-102284-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f0df/6834399/c1f4dd21edce/aging-11-102284-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f0df/6834399/4a5cccee89cf/aging-11-102284-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f0df/6834399/181503d8e1f8/aging-11-102284-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f0df/6834399/8676e9b21579/aging-11-102284-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f0df/6834399/9f050d5cad50/aging-11-102284-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f0df/6834399/67c2cf0b9dd9/aging-11-102284-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f0df/6834399/c1f4dd21edce/aging-11-102284-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f0df/6834399/4a5cccee89cf/aging-11-102284-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f0df/6834399/181503d8e1f8/aging-11-102284-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f0df/6834399/8676e9b21579/aging-11-102284-g006.jpg

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