NOD1 deficiency ameliorates the progression of diabetic retinopathy by modulating bone marrow-retina crosstalk

作者全名："Qiu, Jingwen; Wu, Jing; Chen, Wenwen; Ruan, Yu; Mao, Jingning; Li, Shue; Tang, Xuan; Zhao, Lei; Li, Shengbing; Li, Ke; Liu, Dongfang; Duan, Yaqian"

作者地址："[Qiu, Jingwen; Chen, Wenwen; Tang, Xuan; Li, Shengbing; Li, Ke; Liu, Dongfang; Duan, Yaqian] Chongqing Med Univ, Affiliated Hosp 2, Dept Endocrinol & Metab, Chongqing, Peoples R China; [Wu, Jing] Chongqing Univ, Canc Hosp, Dept Hematol Oncol, Chongqing, Peoples R China; [Ruan, Yu] Chongqing Med Univ, Childrens Hosp, Div Growth Dev & Mental Hlth Children & Adolescenc, Chongqing, Peoples R China; [Mao, Jingning] Chongqing Med Univ, Affiliated Hosp 2, Hlth Med Ctr, Chongqing, Peoples R China; [Li, Shue] Chongqing Med Univ, Affiliated Hosp 2, Dept Lab Med, Chongqing, Peoples R China; [Zhao, Lei] Chongqing Med Univ, Affiliated Hosp 2, Minist Educ, Ctr Lipid Res,Key Lab Mol Biol Infect Dis, Chongqing, Peoples R China"

通信作者："Duan, YQ (通讯作者)，Chongqing Med Univ, Affiliated Hosp 2, Dept Endocrinol & Metab, Chongqing, Peoples R China."

来源：STEM CELL RESEARCH & THERAPY

ESI学科分类：MOLECULAR BIOLOGY & GENETICS

WOS号：WOS:001159749400001

JCR分区：Q1

影响因子：7.5

年份：2024

卷号：15

期号：1

开始页：　

结束页：　

文献类型：Article

关键词：Nucleotide-binding oligomerization domain-containing protein 1; Diabetic retinopathy; Hematopoietic stem/progenitor cells; Macrophage; Inflammation

摘要："BackgroundNucleotide-binding oligomerization domain-containing protein 1 (NOD1) plays a pivotal role in inducing metabolic inflammation in diabetes. Additionally, the NOD1 ligand disrupts the equilibrium of bone marrow-derived hematopoietic stem/progenitor cells, a process that has immense significance in the development of diabetic retinopathy (DR). We hypothesized that NOD1 depletion impedes the advancement of DR by resolving bone marrow dysfunction.MethodsWe generated NOD1-/--Akita double-mutant mice and chimeric mice with hematopoietic-specific NOD1 depletion to study the role of NOD1 in the bone marrow-retina axis.ResultsElevated circulating NOD1 activators were observed in Akita mice after 6 months of diabetes. NOD1 depletion partially restored diabetes-induced structural changes and retinal electrical responses in NOD1-/--Akita mice. Loss of NOD1 significantly ameliorated the progression of diabetic retinal vascular degeneration, as determined by acellular capillary quantification. The preventive effect of NOD1 depletion on DR is linked to bone marrow phenotype alterations, including a restored HSC pool and a shift in hematopoiesis toward myelopoiesis. We also generated chimeric mice with hematopoietic-specific NOD1 ablation, and the results further indicated that NOD1 had a protective effect against DR. Mechanistically, loss of hematopoietic NOD1 resulted in reduced bone marrow-derived macrophage infiltration and decreased CXCL1 and CXCL2 secretion within the retina, subsequently leading to diminished neutrophil chemoattraction and NETosis.ConclusionsThe results of our study unveil, for the first time, the critical role of NOD1 as a trigger for a hematopoietic imbalance toward myelopoiesis and local retinal inflammation, culminating in DR progression. Targeting NOD1 in bone marrow may be a potential strategy for the prevention and treatment of DR."

基金机构：National Natural Science Foundation of China

基金资助正文：No Statement Available