Type 1 diabetes contributes to combined pulmonary fibrosis and emphysema in male alpha 1 antitrypsin deficient mice.
Type 1 diabetes contributes to combined pulmonary fibrosis and emphysema in male alpha 1 antitrypsin deficient mice.
复制标题
DOI：
10.1371/journal.pone.0291948
复制
发表时间：
2023
期刊：
影响因子：
3.7
通讯作者：
中科院分区：
文献类型：
--
作者：
1型糖尿病（T1 D）是一种代谢性疾病，其特征是高血糖，可影响多个器官，导致危及生命的并发症。在T1 D患者中观察到肺部疾病的患病率增加，并且糖尿病是几种肺部病理合并症的主要原因。α-1抗胰蛋白酶（AAT）的缺乏可导致肺气肿的发展。在T1 D患者中记录了AAT血浆浓度和抗蛋白酶活性降低。本研究的目的是确定T1 D是否加剧AAT缺乏症的肺损伤进展。首先，在高血糖症发作后3个月和6个月，研究C57 BL/6 J链脲佐菌素（STZ）诱导的T1 D小鼠的肺功能测试（PFT）和肺组织病理学变化。PFT在STZ注射小鼠的肺中表现出限制性肺模式，沿着促纤维化标志物Acta 2、Ccn 2和Fn 1的mRNA表达上调。在高血糖症发作后6个月观察到胶原沉积增加。为了研究TlD对AAT缺乏背景下肺损伤进展的影响，使用C57 BL/6 J AAT敲除（KO）小鼠。对照组和STZ攻击的AAT KO小鼠在高血糖症发作后3个月肺功能未显示出显著变化。然而，肺的组织学检查表明，增加胶原蛋白的积累和肺泡腔扩大STZ诱导的AAT KO小鼠。对TGF-β刺激的原代肺成纤维细胞的AAT预处理降低促纤维化标志物ACTA 2、CCN 2和FN 1的mRNA表达。在AAT缺乏症中诱导T1 D导致雄性小鼠合并肺纤维化和肺气肿（CPFE）表型。
Type 1 diabetes (T1D) is a metabolic disease characterized by hyperglycemia and can affect multiple organs, leading to life-threatening complications. Increased prevalence of pulmonary disease is observed in T1D patients, and diabetes is a leading cause of comorbidity in several lung pathologies. A deficiency of alpha-1 antitrypsin (AAT) can lead to the development of emphysema. Decreased AAT plasma concentrations and anti-protease activity are documented in T1D patients. The objective of this study was to determine whether T1D exacerbates the progression of lung damage in AAT deficiency. First, pulmonary function testing (PFT) and histopathological changes in the lungs of C57BL/6J streptozotocin (STZ)-induced T1D mice were investigated 3 and 6 months after the onset of hyperglycemia. PFT demonstrated a restrictive pulmonary pattern in the lungs of STZ-injected mice, along with upregulation of mRNA expression of pro-fibrotic markers Acta2, Ccn2, and Fn1. Increased collagen deposition was observed 6 months after the onset of hyperglycemia. To study the effect of T1D on the progression of lung damage in AAT deficiency background, C57BL/6J AAT knockout (KO) mice were used. Control and STZ-challenged AAT KO mice did not show significant changes in lung function 3 months after the onset of hyperglycemia. However, histological examination of the lung demonstrated increased collagen accumulation and alveolar space enlargement in STZ-induced AAT KO mice. AAT pretreatment on TGF-β-stimulated primary lung fibroblasts reduced mRNA expression of pro-fibrotic markers ACTA2, CCN2, and FN1. Induction of T1D in AAT deficiency leads to a combined pulmonary fibrosis and emphysema (CPFE) phenotype in male mice.
Alpha1-抗胰蛋白酶通过抑制TGF-β1诱导的上皮间质转变来减轻肾纤维化。
影响因子：
3.7
作者：
Cho JH;Ryu HM;Oh EJ;Yook JM;Ahn JS;Jung HY;Choi JY;Park SH;Kim YL;Kwak IS;Kim CD
通讯作者：
Kim CD
肿瘤坏死因子α对NOD小鼠胰岛素依赖性糖尿病的影响。 I.自身免疫和糖尿病生成过程的早期发展。
影响因子：
15.3
作者：
Yang, Xiao-Dong;Tisch, Roland;Singer, Steven M.;Cao, Zhu A.;Liblau, Roland S.;Schreiber, Robert D.;McDevitt, Hugh O.
通讯作者：
McDevitt, Hugh O.