Aging increases senescence, calcium signaling, and extracellular matrix deposition in human airway smooth muscle.
Aging increases senescence, calcium signaling, and extracellular matrix deposition in human airway smooth muscle.
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DOI：
10.1371/journal.pone.0254710
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发表时间：
2021
期刊：
影响因子：
3.7
通讯作者：
Prakash YS
中科院分区：
文献类型：
--
作者：
Wicher SA;Roos BB;Teske JJ;Fang YH;Pabelick C;Prakash YS
随着人们年龄的增长和肺部变得僵硬，肺功能下降。随着老年人口的不断增加，了解导致老年肺结构和功能变化的机制非常重要。衰老过程的一部分特征是气道变厚、纤维化程度更高，以及肺实质变化引起的老年性肺气肿。也有衰老，这发生在整个身体的老化。在这里，使用来自不同年龄组患者的人气道平滑肌（ASM）细胞，我们探索了衰老途径和细胞内钙信号传导和细胞外基质（ECM）沉积的变化，以阐明衰老导致肺变厚和变硬的潜在机制。衰老标记物p21、γ H2 AX和β-gal以及一些衰老相关分泌蛋白（SASP）随着衰老而增加，如染色和生化分析所示。激动剂诱导的细胞内Ca 2+反应，测量使用fura-2加载的细胞和荧光成像，随着年龄的增长。然而，生化分析显示，以下标志物的表达随着年龄的增长而下降：M3毒蕈碱受体，TRPC 3，Orai 1，STIM 1，SERCA 2，MMP 2和MMP 9。相反，III型胶原和纤连蛋白沉积随年龄增加。这些数据表明，衰老气道中的衰老增加与作为收缩性标志物的更硬但令人惊讶地更大的细胞内钙信号传导相关。ASM衰老可以在前馈回路中增强纤维化，促进重塑和改变钙储存和缓冲。
Lung function declines as people age and their lungs become stiffer. With an increasing elderly population, understanding mechanisms that contribute to these structural and functional changes in the aging lung is important. Part of the aging process is characterized by thicker, more fibrotic airways, and senile emphysema caused by changes in lung parenchyma. There is also senescence, which occurs throughout the body with aging. Here, using human airway smooth muscle (ASM) cells from patients in different age groups, we explored senescence pathways and changes in intracellular calcium signaling and extracellular matrix (ECM) deposition to elucidate potential mechanisms by which aging leads to thicker and stiffer lungs. Senescent markers p21, γH2AX, and β-gal, and some senescence-associated secretory proteins (SASP) increased with aging, as shown by staining and biochemical analyses. Agonist-induced intracellular Ca2+ responses, measured using fura-2 loaded cells and fluorescence imaging, increased with age. However, biochemical analysis showed that expression of the following markers decreased with age: M3 muscarinic receptor, TRPC3, Orai1, STIM1, SERCA2, MMP2 and MMP9. In contrast, collagen III, and fibronectin deposition increased with age. These data show that senescence increases in the aging airways that is associated with a stiffer but surprisingly greater intracellular calcium signaling as a marker for contractility. ASM senescence may enhance fibrosis in a feed forward loop promoting remodeling and altered calcium storage and buffering.
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影响因子：
64.8
作者：
Baker DJ;Childs BG;Durik M;Wijers ME;Sieben CJ;Zhong J;Saltness RA;Jeganathan KB;Verzosa GC;Pezeshki A;Khazaie K;Miller JD;van Deursen JM
通讯作者：
van Deursen JM
DOI：
10.15252/embj.201592862
发表时间：
2016-04-01
期刊：
The EMBO journal
影响因子：
--
作者：
Correia-Melo C;Marques FD;Anderson R;Hewitt G;Hewitt R;Cole J;Carroll BM;Miwa S;Birch J;Merz A;Rushton MD;Charles M;Jurk D;Tait SW;Czapiewski R;Greaves L;Nelson G;Bohlooly-Y M;Rodriguez-Cuenca S;Vidal-Puig A;Mann D;Saretzki G;Quarato G;Green DR;Adams PD;von Zglinicki T;Korolchuk VI;Passos JF
通讯作者：
Passos JF
DOI：
10.1152/ajplung.00580.2016
发表时间：
2017-08-01
影响因子：
4.9
作者：
Freeman, Michelle R.;Sathish, Venkatachalem;Prakash, Y. S.
通讯作者：
Prakash, Y. S.
DOI：
10.1164/ajrccm.162.2.9907151
发表时间：
2000-08-01
影响因子：
24.7
作者：
Bai, TR;Cooper, J;Weir, TD
通讯作者：
Weir, TD
影响因子：
3.5
作者：
Chapman, James;Fielder, Edward;Passos, Joao F.
通讯作者：
Passos, Joao F.