Pericyte dysfunction and impaired vasomotion are hallmarks of islets during the pathogenesis of type 1 diabetes.
Pericyte dysfunction and impaired vasomotion are hallmarks of islets during the pathogenesis of type 1 diabetes.
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周细胞功能障碍和血管舒缩受损是1型糖尿病发病过程中胰岛的特征。
DOI：
10.1016/j.celrep.2023.112913
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发表时间：
2023-08-29
期刊：
影响因子：
8.8
通讯作者：
中科院分区：
文献类型：
--
作者：
胰岛是内分泌器官，依靠其微血管系统发挥作用。周细胞与内皮细胞一起构成胰岛微血管网络。这些壁细胞对微血管的稳定性和功能至关重要，但它们在1型糖尿病(T1D)的发展过程中是否/如何受到影响尚不清楚。在这里，我们研究了胰岛周细胞密度、表型和功能，这些活的胰腺切片来自无糖尿病的供者、有单一T1D相关自身抗体(GADA+)的供者和最近发病的T1D病例。我们的数据显示，胰岛周细胞和毛细血管对血管活性刺激的反应在T1D早期就受到了损害。微血管功能障碍与胰岛周细胞表型向肌成纤维细胞的转变有关。利用公开的RNA测序(RNA-seq)数据，我们进一步发现与内皮素-1信号和血管和细胞外基质(ECM)重构相关的转录变化是单一自身抗体(Aab)+供体胰腺的特征。我们的数据显示，在胰岛自身免疫的早期阶段就存在微血管功能障碍。Mateus Gonçalves等人。发现在胰岛自身免疫的早期阶段，胰岛周细胞和毛细血管功能失调。在单个Aab+供体胰腺中，存在与内皮素-1信号转导以及血管和ECM重塑相关的几个变化，支持血管系统参与1型糖尿病的发病机制。
Pancreatic islets are endocrine organs that depend on their microvasculature to function. Along with endothelial cells, pericytes comprise the islet microvascular network. These mural cells are crucial for microvascular stability and function, but it is not known if/how they are affected during the development of type 1 diabetes (T1D). Here, we investigate islet pericyte density, phenotype, and function using living pancreas slices from donors without diabetes, donors with a single T1D-associated autoantibody (GADA+), and recent onset T1D cases. Our data show that islet pericyte and capillary responses to vasoactive stimuli are impaired early on in T1D. Microvascular dysfunction is associated with a switch in the phenotype of islet pericytes toward myofibroblasts. Using publicly available RNA sequencing (RNA-seq) data, we further found that transcriptional alterations related to endothelin-1 signaling and vascular and extracellular matrix (ECM) remodeling are hallmarks of single autoantibody (Aab)+ donor pancreata. Our data show that microvascular dysfunction is present at early stages of islet autoimmunity. Mateus Gonçalves et al. found that islet pericytes and capillaries are dysfunctional at early stages of islet autoimmunity. Several alterations related to endothelin-1 signaling and vascular and ECM remodeling are present in single Aab+ donor pancreata, supporting the involvement of the vasculature in type 1 diabetes pathogenesis.
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影响因子：
4.6
作者：
Fontaine AK;Ramirez DG;Littich SF;Piscopio RA;Kravets V;Schleicher WE;Mizoguchi N;Caldwell JH;Weir RFF;Benninger RKP
通讯作者：
Benninger RKP
影响因子：
29
作者：
Coate KC;Cha J;Shrestha S;Wang W;Gonçalves LM;Almaça J;Kapp ME;Fasolino M;Morgan A;Dai C;Saunders DC;Bottino R;Aramandla R;Jenkins R;Stein R;Kaestner KH;Vahedi G;HPAP Consortium;Brissova M;Powers AC
通讯作者：
Powers AC
DOI：
10.1073/pnas.1707702115
发表时间：
2018-06-19
影响因子：
11.1
作者：
Cai, Changsi;Fordsmann, Jonas C.;Lauritzen, Martin J.
通讯作者：
Lauritzen, Martin J.
影响因子：
9.3
作者：
Baron M;Veres A;Wolock SL;Faust AL;Gaujoux R;Vetere A;Ryu JH;Wagner BK;Shen-Orr SS;Klein AM;Melton DA;Yanai I
通讯作者：
Yanai I
影响因子：
4
作者：
Crawford C;Wildman SS;Kelly MC;Kennedy-Lydon TM;Peppiatt-Wildman CM
通讯作者：
Peppiatt-Wildman CM