{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T13:36:12Z","timestamp":1790775372100,"version":"4.1.0"},"reference-count":40,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2023,1,25]],"date-time":"2023-01-25T00:00:00Z","timestamp":1674604800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81630002"],"award-info":[{"award-number":["81630002"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32270662"],"award-info":[{"award-number":["32270662"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["31430047"],"award-info":[{"award-number":["31430047"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82000439"],"award-info":[{"award-number":["82000439"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J cachexia sarcopenia muscle"],"published-print":{"date-parts":[[2023,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Skeletal muscle atrophy is a common condition without a pharmacologic therapy.\n                      <jats:italic>AGGF1<\/jats:italic>\n                      encodes an angiogenic factor that regulates cell differentiation, proliferation, migration, apoptosis, autophagy and endoplasmic reticulum stress, promotes vasculogenesis and angiogenesis and successfully treats cardiovascular diseases. Here, we report the important role of AGGF1 in the pathogenesis of skeletal muscle atrophy and attenuation of muscle atrophy by AGGF1.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      <jats:italic>In vivo<\/jats:italic>\n                      studies were carried out in impaired leg muscles from patients with lumbar disc herniation, two mouse models for skeletal muscle atrophy (denervation and cancer cachexia) and heterozygous\n                      <jats:italic>Aggf1<\/jats:italic>\n                      <jats:sup>\n                        <jats:italic>+\/\u2212<\/jats:italic>\n                      <\/jats:sup>\n                      mice. Mouse muscle atrophy phenotypes were characterized by body weight and myotube cross\u2010sectional areas (CSA) using H&amp;E staining and immunostaining for dystrophin. Molecular mechanistic studies include co\u2010immunoprecipitation (Co\u2010IP), western blotting, quantitative real\u2010time PCR analysis and immunostaining analysis.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Heterozygous\n                      <jats:italic>Aggf1<\/jats:italic>\n                      <jats:sup>\n                        <jats:italic>+\/\u2212<\/jats:italic>\n                      <\/jats:sup>\n                      mice showed exacerbated phenotypes of reduced muscle mass, myotube CSA, MyHC (myosin heavy chain) and \u03b1\u2010actin, increased inflammation (macrophage infiltration), apoptosis and fibrosis after denervation and cachexia. Intramuscular and intraperitoneal injection of recombinant AGGF1 protein attenuates atrophy phenotypes in mice with denervation (gastrocnemius weight 81.3\u00a0\u00b1\u00a05.7\u00a0mg vs. 67.3\u00a0\u00b1\u00a05.1\u00a0mg for AGGF1 vs. buffer;\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0&lt;\u00a00.05) and cachexia (133.7\u00a0\u00b1\u00a04.7 vs. 124.3\u00a0\u00b1\u00a03.2;\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0&lt;\u00a00.05). AGGF1 expression undergoes remodelling and is up\u2010regulated in gastrocnemius and soleus muscles from atrophy mice and impaired leg muscles from patients with lumbar disc herniation by 50\u201360% (\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0&lt;\u00a00.01). Mechanistically, AGGF1 interacts with TWEAK (tumour necrosis factor\u2010like weak inducer of apoptosis), which reduces interaction between TWEAK and its receptor Fn14 (fibroblast growth factor\u2010inducing protein 14). This leads to inhibition of Fn14\u2010induced NF\u2010kappa B (NF\u2010\u03baB) p65 phosphorylation, which reduces expression of muscle\u2010specific E3 ubiquitin ligase MuRF1 (muscle RING finger 1), resulting in increased MyHC and \u03b1\u2010actin and partial reversal of atrophy phenotypes. Autophagy is reduced in\n                      <jats:italic>Aggf1<\/jats:italic>\n                      <jats:sup>\n                        <jats:italic>+\/\u2212<\/jats:italic>\n                      <\/jats:sup>\n                      mice due to inhibition of JNK (c\u2010Jun N\u2010terminal kinase) activation in denervated and cachectic muscles, and AGGF1 treatment enhances autophagy in two atrophy models by activating JNK. In impaired leg muscles of patients with lumbar disc herniation, MuRF1 is up\u2010regulated and MyHC and \u03b1\u2010actin are down\u2010regulated; these effects are reversed by AGGF1 by 50% (\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0&lt;\u00a00.01).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>These results indicate that AGGF1 is a novel regulator for the pathogenesis of skeletal muscle atrophy and attenuates skeletal muscle atrophy by promoting autophagy and inhibiting MuRF1 expression through a molecular signalling pathway of AGGF1\u2010TWEAK\/Fn14\u2010NF\u2010\u03baB. More importantly, the results indicate that AGGF1 protein therapy may be a novel approach to treat patients with skeletal muscle atrophy.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/jcsm.13179","type":"journal-article","created":{"date-parts":[[2023,1,25]],"date-time":"2023-01-25T18:24:16Z","timestamp":1674671056000},"page":"978-991","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["Protein therapy of skeletal muscle atrophy and mechanism by angiogenic factor AGGF1"],"prefix":"10.1002","volume":"14","author":[{"given":"Zuhan","family":"He","sequence":"first","affiliation":[{"name":"Center for Human Genome Research, Key Laboratory of Molecular Biophysics of the Ministry of Education, College of Life Science and Technology Huazhong University of Science and Technology  Wuhan 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