{"doi":"10.1016/j.celrep.2020.108594","title":"ARHGEF3 Regulates Skeletal Muscle Regeneration and Strength through Autophagy","abstract":"Skeletal muscle regeneration after injury is essential for maintaining muscle function throughout aging. ARHGEF3, a RhoA/B-specific GEF, negatively regulates myoblast differentiation through Akt signaling independently of its GEF activity in vitro. Here, we report ARHGEF3's role in skeletal muscle regeneration revealed by ARHGEF3-KO mice. These mice exhibit indiscernible phenotype under basal conditions. Upon acute injury, however, ARHGEF3 deficiency enhances the mass/fiber size and function of regenerating muscles in both young and regeneration-defective middle-aged mice. Surprisingly, these effects occur independently of Akt but via the GEF activity of ARHGEF3. Consistently, overexpression of ARHGEF3 inhibits muscle regeneration in a Rho-associated kinase-dependent manner. We further show that ARHGEF3 KO promotes muscle regeneration through activation of autophagy, a process that is also critical for maintaining muscle strength. Accordingly, ARHGEF3 depletion in old mice prevents muscle weakness by restoring autophagy. Taken together, our findings identify a link between ARHGEF3 and autophagy-related muscle pathophysiology.","journal":"Cell Reports","year":2021,"id":163742,"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":40,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9509,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":436590,"name":"Nilmani Singh","orcid":"0000-0002-3684-7022","position":1,"is_corresponding":false},{"id":569809,"name":"Adriana Reyes‐Ordoñez","orcid":"0000-0003-3482-3841","position":2,"is_corresponding":false},{"id":570452,"name":"Nidhi Khanna","orcid":null,"position":3,"is_corresponding":false},{"id":569810,"name":"Zehua Bao","orcid":"0000-0002-5519-4864","position":4,"is_corresponding":false},{"id":263533,"name":"Huimin Zhao","orcid":"0000-0002-9069-6739","position":5,"is_corresponding":false},{"id":436593,"name":"Jie Chen","orcid":"0000-0002-7887-3747","position":6,"is_corresponding":false},{"id":569808,"name":"Jae‐Sung You","orcid":"0000-0001-7791-8563","position":0,"is_corresponding":true}],"reference_count":49,"raw_metadata":null,"created_at":"2026-07-18T23:45:22.477398Z","pmid":"33406419","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":[]}