Plasma gelsolin levels are associated with diabetes, sex, race, and poverty.
Plasma gelsolin levels are associated with diabetes, sex, race, and poverty.
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DOI：
10.1186/s12967-023-04026-5
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发表时间：
2023-03-10
影响因子：
7.4
通讯作者：
Evans, Michele K. K.
中科院分区：
文献类型：
--
作者：
Noren Hooten, Nicole N.;Mode, Nicolle A. A.;Kowalik, Edward;Omoniyi, Victor;Zonderman, Alan B. B.;Ezike, Ngozi;DiNubile, Mark J. J.;Levinson, Susan K. L.;Evans, Michele K. K.
关键词：
炎症相关代谢性疾病-2型糖尿病的日益流行，给我们提出了一个挑战，即如何更好地了解预防或更好地控制这种与年龄相关的疾病的潜在机制或生物标志物。作为细胞外肌动蛋白清除系统的一部分，明胶蛋白异构体被分泌到血浆中，该系统通过消化和去除从受损细胞释放的肌动蛋白细丝来起到保护作用。最近的数据表明，血浆明胶蛋白(PGSN)水平降低可以作为炎症条件的生物标志物。细胞外小泡(EVS)是一组异质性的细胞膜结构，参与细胞间信号转导，与包括2型糖尿病在内的代谢和炎症性疾病有关。我们研究了pGSN水平是否与EV浓度和炎性血浆蛋白在糖尿病或非糖尿病患者中相关。我们对患有和不患有糖尿病的中年非裔美国人和白人研究参与者进行了纵向量化(n = 104)。用双抗体夹心法测定血浆明胶蛋白水平。EV浓度(亚队列n = 40)通过纳米颗粒跟踪分析进行测量。在SomaScan®v4蛋白质组平台上检测炎性血浆蛋白。男性的pGSN水平低于女性。与没有糖尿病的白人和患有或不患有糖尿病的非裔美国人相比，患有糖尿病的白人个体的pGSN水平明显较低。对于生活在贫困以下的成年人来说，患有糖尿病的人的pGSN水平低于没有糖尿病的人。生活在贫困之上的成年人无论处于何种糖尿病状态，其pGSN水平都相似。EV浓度与pGSN水平之间无相关性(r = − 为0.03；p = 为0.85)。大规模探索性血浆蛋白蛋白质组学发现了47种蛋白质，这些蛋白质在糖尿病状态下存在显著差异，其中19种蛋白质与pGSN水平显著相关，包括脂联素。在这群不同种族的糖尿病患者和非糖尿病患者中，我们发现pGSN水平在糖尿病状态、性别、种族和贫困方面存在差异。我们还报道了pGSN与脂肪因子、脂联素以及其他炎症和糖尿病相关蛋白的显著相关性。这些数据提供了对pGSN和糖尿病关系的机械性见解。
The growing epidemic of the inflammation-related metabolic disease, type 2 diabetes mellitus, presents a challenge to improve our understanding of potential mechanisms or biomarkers to prevent or better control this age-associated disease. A gelsolin isoform is secreted into the plasma as part of the extracellular actin scavenger system which serves a protective role by digesting and removing actin filaments released from damaged cells. Recent data indicate a role for decreased plasma gelsolin (pGSN) levels as a biomarker of inflammatory conditions. Extracellular vesicles (EVs), a heterogeneous group of cell-derived membranous structures involved in intercellular signaling, have been implicated in metabolic and inflammatory diseases including type 2 diabetes mellitus. We examined whether pGSN levels were associated with EV concentration and inflammatory plasma proteins in individuals with or without diabetes. We quantified pGSN longitudinally (n = 104) in a socioeconomically diverse cohort of middle-aged African American and White study participants with and without diabetes mellitus. Plasma gelsolin levels were assayed by ELISA. EV concentration (sub-cohort n = 40) was measured using nanoparticle tracking analysis. Inflammatory plasma proteins were assayed on the SomaScan® v4 proteomic platform. pGSN levels were lower in men than women. White individuals with diabetes had significantly lower levels of pGSN compared to White individuals without diabetes and to African American individuals either with or without diabetes. For adults living below poverty, those with diabetes had lower pGSN levels than those without diabetes. Adults living above poverty had similar pGSN levels regardless of diabetes status. No correlation between EV concentrations and pGSN levels was identified (r = − 0.03; p = 0.85). Large-scale exploratory plasma protein proteomics revealed 47 proteins that significantly differed by diabetes status, 19 of which significantly correlated with pGSN levels, including adiponectin. In this cohort of racially diverse individuals with and without diabetes, we found differences in pGSN levels with diabetes status, sex, race, and poverty. We also report significant associations of pGSN with the adipokine, adiponectin, and other inflammation- and diabetes-related proteins. These data provide mechanistic insights into the relationship of pGSN and diabetes.
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DOI：
10.1126/science.aau6977
发表时间：
2020-02-07
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Kalluri R;LeBleu VS
通讯作者：
LeBleu VS
DOI：
10.1002/wrna.1413
发表时间：
2017-07
期刊：
Wiley interdisciplinary reviews. RNA
影响因子：
--
作者：
Kim KM;Abdelmohsen K;Mustapic M;Kapogiannis D;Gorospe M
通讯作者：
Gorospe M
影响因子：
2.9
作者：
Davoodian, K;Ritchings, BW;Bubb, MR
通讯作者：
Bubb, MR
影响因子：
11.8
作者：
Self, Wesley H.;Wunderink, Richard G.;Grijalva, Carlos G.
通讯作者：
Grijalva, Carlos G.
影响因子：
5.5
作者：
Noren Hooten, Nicole;Evans, Michele K.
通讯作者：
Evans, Michele K.