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Long‐noncoding RNA Atrolnc‐1 promotes muscle wasting in mice with chronic kidney disease
Background Chronic kidney disease (CKD) is commonly associated with cachexia, a condition that causes skeletal muscle wasting and an unfavourable prognosis. Although mechanisms leading to cachexia have been intensively studied, the advance of biological knowledges and technologies encourages us to m...
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Published in: | Journal of cachexia, sarcopenia and muscle sarcopenia and muscle, 2018-10, Vol.9 (5), p.962-974 |
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Main Authors: | , , , , , , , |
Format: | Article |
Language: | English |
Subjects: | |
Citations: | Items that this one cites Items that cite this one |
Online Access: | Get full text |
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Summary: | Background
Chronic kidney disease (CKD) is commonly associated with cachexia, a condition that causes skeletal muscle wasting and an unfavourable prognosis. Although mechanisms leading to cachexia have been intensively studied, the advance of biological knowledges and technologies encourages us to make progress in understanding the pathogenesis of this disorder. Long noncoding RNAs (lncRNAs) are defined as >200 nucleotides RNAs but lack the protein‐coding potential. LncRNAs are involved in the pathogenesis of many diseases, but whether they functionally involve in muscle protein loss has not been investigated.
Methods
We performed lncRNA array and identified an lncRNA, which we named Atrolnc‐1, remarkably elevated in atrophying muscles from mice with cachexia. We examined how overexpression or knockdown of Atrolnc‐1 could influence muscle protein synthesis and degradation. We also examined whether inhibition of Atrolnc‐1 ameliorates muscle wasting in mice with CKD.
Results
We documented that Atrolnc‐1 expression is continuously increased in muscles of mice with fasting (5.4 fold), cancer (2.0 fold), or CKD (5.1 fold). We found that depressed insulin signalling stimulates the transcription factor C/EBP‐α binding to the promoter of Atrolnc‐1 and promotes the expression of Atrolnc‐1. In cultured C2C12 myotubes, overexpression of Atrolnc‐1 increases protein degradation (0.45±0.03 vs. 0.64±0.02, *p |
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ISSN: | 2190-5991 2190-6009 |
DOI: | 10.1002/jcsm.12321 |