期刊
JOURNAL OF CLINICAL INVESTIGATION
卷 131, 期 11, 页码 -出版社
AMER SOC CLINICAL INVESTIGATION INC
DOI: 10.1172/JCI135821
关键词
-
资金
- Else Kroner-Fresenius Foundation
- George M. O'Brien Michigan Kidney Translational Core Center - NIH/National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) [2P30-DK-081943]
- NIH/NIDDK [U2C DK114886, UH3DK114861, UH3DK114866, UH3DK114870, UH3DK114908, UH3DK114915, UH3DK114926, UH3DK114907, UH3DK114920, UH3DK114923, UH3DK114933, UH3DK114937]
- Deutsche Forschungsgemeinschaft (DFG) [CRC1192]
- DFG [CRC1192, OS 196/4-1, 322900939, 432698239, 454024652, KR1984/4-1, HU 1016/8-2, HU 1016/11-1, HU 1016/12-1]
- German Federal Ministry of Education and Research [BMBF: STOPFSGS-01GM1901A]
- European Research Council (ERC) under the European Union [101001791]
- Agenzia Spaziale Italiana (MARS-PRE)
- Associazione Italiana Ricerca sul Cancro [23257]
- Deutsche Gesellschaft fur Nephrologie
- eMed Consortia Fibromap (BMBF)
- BMBF [STOP-FSGS-01GM1901C, NephrESA-031L0191E]
- Else-Kroner Fresenius Foundation (Else KronerPromotionskolleg-iPRIME)
- ERC [616891]
- Horizon 2020-Innovative Medicines Initiative2 consortium Biomarker Enterprise [115974]
- European Union's Horizon 2020 research and innovation program
- European Federation of Pharmaceutical Industries and Associations
- Juvenile Diabetes Research Foundation
- Deutsche Forschungsgemeinschaft (DFG
- Heisenberg Programme)
- European Research Council (ERC) [616891] Funding Source: European Research Council (ERC)
- BBSRC [BB/J016454/1] Funding Source: UKRI
This study investigated the mechanism of skeletal muscle wasting in CKD and found that the soluble pro-cachectic factor activin A is expressed in specific kidney cell populations, proposing a vicious signaling cycle between kidney and muscle. Blocking activin A signaling pharmacologically prevented muscle wasting in experimental CKD mouse models.
Skeletal muscle wasting is commonly associated with chronic kidney disease (CKD), resulting in increased morbidity and mortality. However, the link between kidney and muscle function remains poorly understood. Here, we took a complementary interorgan approach to investigate skeletal muscle wasting in CKD. We identified increased production and elevated blood levels of soluble pro-cachectic factors, including activin A, directly linking experimental and human CKD to skeletal muscle wasting programs. Single-cell sequencing data identified the expression of activin A in specific kidney cell populations of fibroblasts and cells of the juxtaglomerular apparatus. We propose that persistent and increased kidney production of procachectic factors, combined with a lack of kidney clearance, facilitates a vicious kidney/muscle signaling cycle, leading to exacerbated blood accumulation and, thereby, skeletal muscle wasting. Systemic pharmacological blockade of activin A using soluble activin receptor type IIB ligand trap as well as muscle-specific adeno-associated virus-mediated downregulation of its receptor ACVR2A/B prevented muscle wasting in different mouse models of experimental CKD, suggesting that activin A is a key factor in CKD-induced cachexia. In summary, we uncovered a crosstalk between kidney and muscle and propose modulation of activin signaling as a potential therapeutic strategy for skeletal muscle wasting in CKD.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据