Pro-cachectic factors link experimental and human chronic kidney disease to skeletal muscle wasting programs

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Solagna , F , Tezze , C , Lindenmeyer , M T , Lu , S , Wu , G , Liu , S , Zhao , Y , Mitchell , R , Meyer , C , Omairi , S , Kilic , T , Paolini , A , Ritvos , O , Pasternack , A , Matsakas , A , Kylies , D , zur Wiesch , J S , Turner , J-E , Wanner , N , Nair , V , Eichinger , F , Menon , R , Martin , I V , Klinkhammer , B M , Hoxha , E , Cohen , C D , Tharaux , P-L , Boor , P , Ostendorf , T , Kretzler , M , Sandri , M , Kretz , O , Puelles , V G , Patel , K & Huber , T B 2021 , ' Pro-cachectic factors link experimental and human chronic kidney disease to skeletal muscle wasting programs ' , Journal of Clinical Investigation , vol. 131 , no. 11 , 135821 . https://doi.org/10.1172/JCI135821

Title: Pro-cachectic factors link experimental and human chronic kidney disease to skeletal muscle wasting programs
Author: Solagna, Francesca; Tezze, C.; Lindenmeyer, M.T.; Lu, S.; Wu, G.; Liu, S.; Zhao, Y.; Mitchell, R.; Meyer, C.; Omairi, S.; Kilic, T.; Paolini, A.; Ritvos, O.; Pasternack, A.; Matsakas, A.; Kylies, D.; zur Wiesch, J.S.; Turner, J.-E.; Wanner, N.; Nair, V.; Eichinger, F.; Menon, R.; Martin, I.V.; Klinkhammer, B.M.; Hoxha, E.; Cohen, C.D.; Tharaux, P.-L.; Boor, P.; Ostendorf, T.; Kretzler, M.; Sandri, M.; Kretz, O.; Puelles, V.G.; Patel, K.; Huber, T.B.
Contributor organization: Department of Physiology
Growth factor physiology
Faculty of Medicine
University of Helsinki
Medicum
Date: 2021-06-01
Language: eng
Number of pages: 18
Belongs to series: Journal of Clinical Investigation
ISSN: 0021-9738
DOI: https://doi.org/10.1172/JCI135821
URI: http://hdl.handle.net/10138/332421
Abstract: 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.
Description: cited By 1
Subject: 3121 General medicine, internal medicine and other clinical medicine
PERICYTE-MYOFIBROBLAST TRANSITION
ACTIVIN-A
CANCER CACHEXIA
MOLECULAR-MECHANISMS
II RECEPTORS
FIBROSIS
MASS
HOMEOSTASIS
SARCOPENIA
MYOSTATIN
Peer reviewed: Yes
Usage restriction: openAccess
Self-archived version: publishedVersion


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