TWEAK Regulates Muscle Functions in a Mouse Model of RNA Toxicity.
Myotonic dystrophy type 1 (DM1), the most common form of muscular dystrophy in adults, is caused by toxic RNAs produced from the mutant DM protein kinase (DMPK) gene. DM1 is characterized by progressive muscle wasting and weakness. Therapeutic strategies have mainly focused on targeting the toxic RN...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2016-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC4762946?pdf=render |
| _version_ | 1819225113725239296 |
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| author | Ramesh S Yadava Erin P Foff Qing Yu Jordan T Gladman Timothy S Zheng Mani S Mahadevan |
| author_facet | Ramesh S Yadava Erin P Foff Qing Yu Jordan T Gladman Timothy S Zheng Mani S Mahadevan |
| author_sort | Ramesh S Yadava |
| collection | DOAJ |
| description | Myotonic dystrophy type 1 (DM1), the most common form of muscular dystrophy in adults, is caused by toxic RNAs produced from the mutant DM protein kinase (DMPK) gene. DM1 is characterized by progressive muscle wasting and weakness. Therapeutic strategies have mainly focused on targeting the toxic RNA. Previously, we found that fibroblast growth factor-inducible 14 (Fn14), the receptor for TWEAK, is induced in skeletal muscles and hearts of mouse models of RNA toxicity and that blocking TWEAK/Fn14 signaling improves muscle function and histology. Here, we studied the effect of Tweak deficiency in a RNA toxicity mouse model. The genetic deletion of Tweak in these mice significantly reduced muscle damage and improved muscle function. In contrast, administration of TWEAK in the RNA toxicity mice impaired functional outcomes and worsened muscle histopathology. These studies show that signaling via TWEAK is deleterious to muscle in RNA toxicity and support the demonstrated utility of anti-TWEAK therapeutics. |
| first_indexed | 2024-12-23T10:04:26Z |
| format | Article |
| id | doaj.art-da8d9ca5a0f248d4b35c01403e596705 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-23T10:04:26Z |
| publishDate | 2016-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-da8d9ca5a0f248d4b35c01403e5967052022-12-21T17:51:08ZengPublic Library of Science (PLoS)PLoS ONE1932-62032016-01-01112e015019210.1371/journal.pone.0150192TWEAK Regulates Muscle Functions in a Mouse Model of RNA Toxicity.Ramesh S YadavaErin P FoffQing YuJordan T GladmanTimothy S ZhengMani S MahadevanMyotonic dystrophy type 1 (DM1), the most common form of muscular dystrophy in adults, is caused by toxic RNAs produced from the mutant DM protein kinase (DMPK) gene. DM1 is characterized by progressive muscle wasting and weakness. Therapeutic strategies have mainly focused on targeting the toxic RNA. Previously, we found that fibroblast growth factor-inducible 14 (Fn14), the receptor for TWEAK, is induced in skeletal muscles and hearts of mouse models of RNA toxicity and that blocking TWEAK/Fn14 signaling improves muscle function and histology. Here, we studied the effect of Tweak deficiency in a RNA toxicity mouse model. The genetic deletion of Tweak in these mice significantly reduced muscle damage and improved muscle function. In contrast, administration of TWEAK in the RNA toxicity mice impaired functional outcomes and worsened muscle histopathology. These studies show that signaling via TWEAK is deleterious to muscle in RNA toxicity and support the demonstrated utility of anti-TWEAK therapeutics.http://europepmc.org/articles/PMC4762946?pdf=render |
| spellingShingle | Ramesh S Yadava Erin P Foff Qing Yu Jordan T Gladman Timothy S Zheng Mani S Mahadevan TWEAK Regulates Muscle Functions in a Mouse Model of RNA Toxicity. PLoS ONE |
| title | TWEAK Regulates Muscle Functions in a Mouse Model of RNA Toxicity. |
| title_full | TWEAK Regulates Muscle Functions in a Mouse Model of RNA Toxicity. |
| title_fullStr | TWEAK Regulates Muscle Functions in a Mouse Model of RNA Toxicity. |
| title_full_unstemmed | TWEAK Regulates Muscle Functions in a Mouse Model of RNA Toxicity. |
| title_short | TWEAK Regulates Muscle Functions in a Mouse Model of RNA Toxicity. |
| title_sort | tweak regulates muscle functions in a mouse model of rna toxicity |
| url | http://europepmc.org/articles/PMC4762946?pdf=render |
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