Primary skeletal muscle cells from chronic kidney disease patients retain hallmarks of cachexia in vitro

Autor: Luke A. Baker, Thomas F. O'Sullivan, Katherine A. Robinson, Matthew P.M. Graham‐Brown, Rupert W. Major, Robert U. Ashford, Alice C. Smith, Andrew Philp, Emma L. Watson
Jazyk: angličtina
Rok vydání: 2022
Předmět:
Zdroj: Journal of Cachexia, Sarcopenia and Muscle, Vol 13, Iss 2, Pp 1238-1249 (2022)
Druh dokumentu: article
ISSN: 2190-6009
2190-5991
DOI: 10.1002/jcsm.12802
Popis: Abstract Background Skeletal muscle wasting and dysfunction are common characteristics noted in people who suffer from chronic kidney disease (CKD). The mechanisms by which this occurs are complex, and although progress has been made, the key underpinning mechanisms are not yet fully elucidated. With work to date primarily conducted in nephrectomy‐based animal models, translational capacity to our patient population has been challenging. This could be overcome if rationale developing work could be conducted in human based models with greater translational capacity. This could be achieved using cells derived from patient biopsies, if they retain phenotypic traits noted in vivo. Methods Here, we performed a systematic characterization of CKD derived muscle cells (CKD; n = 10; age: 54.40 ± 15.53 years; eGFR: 22.25 ± 13.22 ml/min/1.73 m2) in comparison with matched controls (CON; n = 10; age: 58.66 ± 14.74 years; eGFR: 85.81 ± 8.09 ml/min/1.73 m2 ). Harvested human derived muscle cells (HDMCs) were taken through proliferative and differentiation phases and investigated in the context of myogenic progression, inflammation, protein synthesis, and protein breakdown. Follow up investigations exposed HDMC myotubes from each donor type to 0, 0.4, and 100 nM of IGF‐1 in order to investigate any differences in anabolic resistance. Results Harvested human derived muscle cells isolated from CKD patients displayed higher rates of protein degradation (P = 0.044) alongside elevated expression of both TRIM63 (2.28‐fold higher, P = 0.054) and fbox32 (6.4‐fold higher, P 0.05); however, CKD derived cells displayed a significant degree of anabolic resistance in response to IGF‐1 stimulation (both doses) in comparison with matched CONs (0.4 nm: P
Databáze: Directory of Open Access Journals
Externí odkaz: