Myoglobin-derived iron causes wound enlargement and impaired regeneration in pressure injuries of muscle
The reasons for poor healing of pressure injuries are poorly understood. Vascular ulcers are worsened by extracellular release of hemoglobin, so we examined the impact of myoglobin (Mb) iron in murine muscle pressure injuries (mPI). Tests used Mb-knockout or treatment with deferoxamine iron chelator...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2023-06-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/85633 |
| _version_ | 1797813331013140480 |
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| author | Nurul Jannah Mohamed Nasir Hans Heemskerk Julia Jenkins Nur Hidayah Hamadee Ralph Bunte Lisa Tucker-Kellogg |
| author_facet | Nurul Jannah Mohamed Nasir Hans Heemskerk Julia Jenkins Nur Hidayah Hamadee Ralph Bunte Lisa Tucker-Kellogg |
| author_sort | Nurul Jannah Mohamed Nasir |
| collection | DOAJ |
| description | The reasons for poor healing of pressure injuries are poorly understood. Vascular ulcers are worsened by extracellular release of hemoglobin, so we examined the impact of myoglobin (Mb) iron in murine muscle pressure injuries (mPI). Tests used Mb-knockout or treatment with deferoxamine iron chelator (DFO). Unlike acute injuries from cardiotoxin, mPI regenerated poorly with a lack of viable immune cells, persistence of dead tissue (necro-slough), and abnormal deposition of iron. However, Mb-knockout or DFO-treated mPI displayed a reversal of the pathology: decreased tissue death, decreased iron deposition, decrease in markers of oxidative damage, and higher numbers of intact immune cells. Subsequently, DFO treatment improved myofiber regeneration and morphology. We conclude that myoglobin iron contributes to tissue death in mPI. Remarkably, a large fraction of muscle death in untreated mPI occurred later than, and was preventable by, DFO treatment, even though treatment started 12 hr after pressure was removed. This demonstrates an opportunity for post-pressure prevention to salvage tissue viability. |
| first_indexed | 2024-03-13T07:51:22Z |
| format | Article |
| id | doaj.art-ba1d7352c0354b1c83701d9c073db731 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-03-13T07:51:22Z |
| publishDate | 2023-06-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-ba1d7352c0354b1c83701d9c073db7312023-06-02T15:46:39ZengeLife Sciences Publications LtdeLife2050-084X2023-06-011210.7554/eLife.85633Myoglobin-derived iron causes wound enlargement and impaired regeneration in pressure injuries of muscleNurul Jannah Mohamed Nasir0https://orcid.org/0000-0003-3700-9036Hans Heemskerk1Julia Jenkins2Nur Hidayah Hamadee3https://orcid.org/0009-0002-8993-8419Ralph Bunte4Lisa Tucker-Kellogg5https://orcid.org/0000-0002-1301-7069Cancer & Stem Cell Biology, Duke-NUS Medical School, Singapore, Singapore; Centre for Computational Biology, Duke-NUS Medical School, Singapore, SingaporeCancer & Stem Cell Biology, Duke-NUS Medical School, Singapore, Singapore; BioSyM and CAMP Interdisciplinary Research Group, Singapore-MIT Alliance for Research and Technology, CREATE, Singapore, SingaporeCancer & Stem Cell Biology, Duke-NUS Medical School, Singapore, SingaporeCancer & Stem Cell Biology, Duke-NUS Medical School, Singapore, SingaporeCancer & Stem Cell Biology, Duke-NUS Medical School, Singapore, SingaporeCancer & Stem Cell Biology, Duke-NUS Medical School, Singapore, Singapore; Centre for Computational Biology, Duke-NUS Medical School, Singapore, Singapore; BioSyM and CAMP Interdisciplinary Research Group, Singapore-MIT Alliance for Research and Technology, CREATE, Singapore, SingaporeThe reasons for poor healing of pressure injuries are poorly understood. Vascular ulcers are worsened by extracellular release of hemoglobin, so we examined the impact of myoglobin (Mb) iron in murine muscle pressure injuries (mPI). Tests used Mb-knockout or treatment with deferoxamine iron chelator (DFO). Unlike acute injuries from cardiotoxin, mPI regenerated poorly with a lack of viable immune cells, persistence of dead tissue (necro-slough), and abnormal deposition of iron. However, Mb-knockout or DFO-treated mPI displayed a reversal of the pathology: decreased tissue death, decreased iron deposition, decrease in markers of oxidative damage, and higher numbers of intact immune cells. Subsequently, DFO treatment improved myofiber regeneration and morphology. We conclude that myoglobin iron contributes to tissue death in mPI. Remarkably, a large fraction of muscle death in untreated mPI occurred later than, and was preventable by, DFO treatment, even though treatment started 12 hr after pressure was removed. This demonstrates an opportunity for post-pressure prevention to salvage tissue viability.https://elifesciences.org/articles/85633chronic wound healingischemic muscle deathferroptosismyogenesisregenerative medicinestem cells |
| spellingShingle | Nurul Jannah Mohamed Nasir Hans Heemskerk Julia Jenkins Nur Hidayah Hamadee Ralph Bunte Lisa Tucker-Kellogg Myoglobin-derived iron causes wound enlargement and impaired regeneration in pressure injuries of muscle eLife chronic wound healing ischemic muscle death ferroptosis myogenesis regenerative medicine stem cells |
| title | Myoglobin-derived iron causes wound enlargement and impaired regeneration in pressure injuries of muscle |
| title_full | Myoglobin-derived iron causes wound enlargement and impaired regeneration in pressure injuries of muscle |
| title_fullStr | Myoglobin-derived iron causes wound enlargement and impaired regeneration in pressure injuries of muscle |
| title_full_unstemmed | Myoglobin-derived iron causes wound enlargement and impaired regeneration in pressure injuries of muscle |
| title_short | Myoglobin-derived iron causes wound enlargement and impaired regeneration in pressure injuries of muscle |
| title_sort | myoglobin derived iron causes wound enlargement and impaired regeneration in pressure injuries of muscle |
| topic | chronic wound healing ischemic muscle death ferroptosis myogenesis regenerative medicine stem cells |
| url | https://elifesciences.org/articles/85633 |
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