Peptidoglycan-Mediated Bone Marrow Autonomic Neuropathy Impairs Hematopoietic Stem/Progenitor Cells via a NOD1-Dependent Pathway in db/db Mice.
Peptidoglycan-Mediated Bone Marrow Autonomic Neuropathy Impairs Hematopoietic Stem/Progenitor Cells via a NOD1-Dependent Pathway in db/db Mice.
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DOI：
10.1155/2022/4249843
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发表时间：
2022
影响因子：
4.3
通讯作者：
Duan, Yaqian
中科院分区：
文献类型：
--
作者：
Wu, Jing;Zhang, Binghan;Li, Shengbing;Chen, Wenwen;Mao, Jinning;Li, Ke;Liu, Dongfang;Duan, Yaqian
骨髓源性造血干/祖细胞（HSPC）的损伤有助于糖尿病受试者血管并发症的进展。极少量的细菌来源的病原体相关分子模式（PAMP）建立骨髓细胞库。我们假设PAMP肽聚糖（PGN）的改变加剧了糖尿病患者的HSPC功能障碍。我们观察到糖尿病小鼠骨髓中PGN浸润增加。外源性给予PGN选择性地减少了db/db小鼠骨髓中长期再生造血干细胞（LT-HSC）的数量，并伴有血管修复功能受损。我们进一步揭示了骨髓去神经支配导致了PGN相关的HSPC功能障碍。NOD 1的抑制改善了PGN诱导的骨髓自主神经病变，这显著地恢复了HSPC池和体内功能。这些数据首次揭示了PGN作为肠-骨髓轴上的关键因素，在糖尿病背景下促进骨髓去神经支配和HSPC调节。
Impairment of bone marrow-derived hematopoietic stem/progenitor cells (HSPCs) contributes to the progression of vascular complications in subjects with diabetes. Very small amounts of bacterial-derived pathogen-associated molecular patterns (PAMPs) establish the bone marrow cell pool. We hypothesize that alteration of the PAMP peptidoglycan (PGN) exacerbates HSPC dysfunction in diabetes. We observed increased PGN infiltration in the bone marrow of diabetic mice. Exogenous administration of PGN selectively reduced the number of long-term repopulating hematopoietic stem cells (LT-HSCs), accompanied by impaired vasoreparative functions in db/db mouse bone marrow. We further revealed that bone marrow denervation contributed to PGN-associated HSPC dysfunction. Inhibition of NOD1 ameliorated PGN-induced bone marrow autonomic neuropathy, which significantly rejuvenated the HSPC pools and functions in vivo. These data reveal for the first time that PGN, as a critical factor on the gut-bone marrow axis, promotes bone marrow denervation and HSPC modulation in the context of diabetes.
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影响因子：
11.1
作者：
Andriessen EM;Wilson AM;Mawambo G;Dejda A;Miloudi K;Sennlaub F;Sapieha P
通讯作者：
Sapieha P
影响因子：
40.5
作者：
Antonetti, David A.;Silva, Paolo S.;Stitt, Alan W.
通讯作者：
Stitt, Alan W.
影响因子：
23.9
作者：
Liu Y;Elf SE;Miyata Y;Sashida G;Liu Y;Huang G;Di Giandomenico S;Lee JM;Deblasio A;Menendez S;Antipin J;Reva B;Koff A;Nimer SD
通讯作者：
Nimer SD
影响因子：
39.3
作者：
Fadini, Gian Paolo;Vigili de Kreutzenberg, Saula;Avogaro, Angelo
通讯作者：
Avogaro, Angelo
影响因子：
7.3
作者：
Arroyo DS;Gaviglio EA;Peralta Ramos JM;Bussi C;Avalos MP;Cancela LM;Iribarren P
通讯作者：
Iribarren P