{"doi":"10.1113/jp288982","title":"Effects of inhibition of Janus kinase signalling during controlled mechanical ventilation on the rate of skeletal muscle protein synthesis","abstract":"Abstract We employed a unique murine intensive care unit (ICU) model allowing long‐term studies of the ICU condition (immobilization, paralysis, sedation and mechanical ventilation). This model resulted in a substantial loss of myofibrillar protein and muscle size. We hypothesized that an inhibitor of Janus kinase (JAK) activation of transcription 3 (STAT3 (signal transducer and activator of transcription 3)) phosphorylation would help to preserve muscle mass by stimulating the rate of protein synthesis. Sprague–Dawley rats were divided into a control group (CON, n = 5) and two groups exposed to the ICU condition for 8 days. One group was treated with a JAK/STAT3 inhibitor (JST, n = 5) and one without a JST (immobilized group, n = 3) inhibitor. To measure the fractional synthesis rate (FSR) of proteins across the muscle proteome, 2 H 2 O was administered as an intraparitoneal (IP) bolus followed by continuous infusion of 8% 2 H 2 O to maintain body water enrichment. Soleus, extensor digitorum longus (EDL), tibialis anterior (TA), gastrocnemius and diaphragm were obtained from all animals. Liquid chromatography–mass spectrometry (LC/MS–MS) analysis was used to measure protein FSR. Compared to CON myofibrillar protein FSR was decreased 39%–73%, with the decrease in gastrocnemius > soleus > TA > diaphragm > EDL. Sarcoplasmic protein FSR was decreased 38%–69%, with the decrease in gastrocnemius > TA > EDL > soleus > diaphragm. Mitochondrial protein FSR was decreased 34%–52%, with the decrease in TA > soleus > gastrocnemius > EDL > diaphragm. The decreases in protein flux rates by ontology corresponded broadly with function and fibre types. Immobilization resulted in profound and tissue‐specific decreases in protein FSR, with JAK/STAT3 showing a significant effect to preserve FSR, muscle mass and body weight. image Key points Mechanical silencing of skeletal muscle resulted in a large lowering of protein fractional synthesis rate (FSR) in all muscles measured, the extent of which was muscle‐ and fibre specific. All muscle protein ontologies were affected. A Janus kinase (JAK)/STAT inhibitor had a positive effect on body mass, muscle size and protein FSR.","journal":"The Journal of Physiology","year":2025,"id":536808,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.972,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":677968,"name":"Mahalakshmi Shankaran","orcid":"0000-0001-9138-9610","position":1,"is_corresponding":false},{"id":660121,"name":"Lars Larsson","orcid":"0000-0003-3722-035X","position":2,"is_corresponding":false},{"id":1422120,"name":"Nicola Cacciani","orcid":"0000-0002-0373-7249","position":3,"is_corresponding":false},{"id":1422647,"name":"Yvette Hedström","orcid":null,"position":4,"is_corresponding":false},{"id":106952,"name":"James L. Kirkland","orcid":"0000-0003-1676-4905","position":5,"is_corresponding":false},{"id":106953,"name":"Tamar Tchkonia","orcid":"0000-0003-4623-7145","position":6,"is_corresponding":false},{"id":733438,"name":"Hussein Mohammed","orcid":"0000-0002-9963-7129","position":7,"is_corresponding":false},{"id":677969,"name":"Tyler Field","orcid":"0000-0001-5098-8932","position":8,"is_corresponding":false},{"id":292054,"name":"Marc K. Hellerstein","orcid":"0000-0002-2327-0834","position":9,"is_corresponding":false},{"id":278796,"name":"William J. Evans","orcid":"0000-0001-6757-1471","position":0,"is_corresponding":true}],"reference_count":34,"raw_metadata":null,"created_at":"2026-07-19T02:52:09.056872Z","pmid":"41043078","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}