| RRC ID |
87712
|
| 著者 |
Chowdhury K, Huang CL, Lin IT, Hung YJ, Lim KL, Liu HW, Wei KH, Yang KC, Chang YM, Lai BS.
|
| タイトル |
Immune modulation promotes heart regeneration through macrophage and Granulin functions in medaka.
|
| ジャーナル |
Proc Natl Acad Sci U S A
|
| Abstract |
Myocardial infarction results in irreversible cardiomyocyte loss and fibrotic remodeling in adult mammals, whereas some vertebrates retain the ability to regenerate cardiac tissue. Comparative studies suggest that immune responses critically influence repair outcomes, yet the immune programs associated with regeneration remain incompletely defined. Here, we investigate how immune modulation accelerates cardiac repair in the nonregenerative medaka (Oryzias latipes). Using bulk and single-cell transcriptomics combined with functional assays, we show that stimulation with the Toll-like receptor 3 agonist poly I:C accelerates early immune activation and enhances macrophage-dependent debris clearance, associated with inflammatory resolution after cardiac injury. Single-cell analysis of enriched myeloid populations identifies regeneration-associated macrophage subsets characterized by phagocytic and immune-regulatory gene programs, including elevated expression of granulin-a (grna). Spatial analysis by hybridization chain reaction reveals increased numbers of grna-expressing macrophages in the injury border zone, coinciding with the regenerative niche of cardiomyocyte proliferation. Consistent with these findings, administration of recombinant Granulin A enhances cardiomyocyte proliferation and reduces scar burden in medaka hearts. Together, these findings indicate that immune modulation reshapes macrophage functional states during cardiac repair and link macrophage-associated granulin expression to regenerative outcomes, highlighting macrophage properties as a potential target for improving heart repair.
|
| 巻・号 |
123(16)
|
| ページ |
e2524705123
|
| 公開日 |
2026-4-21
|
| DOI |
10.1073/pnas.2524705123
|
| PMID |
41980096
|
| PMC |
PMC13099641
|
| MeSH |
Animals
Cell Proliferation
Granulins* / genetics
Granulins* / immunology
Granulins* / metabolism
Heart* / physiology
Macrophages* / immunology
Macrophages* / metabolism
Myocardium / immunology
Myocytes, Cardiac / immunology
Myocytes, Cardiac / metabolism
Oryzias* / immunology
Poly I-C / pharmacology
Regeneration* / immunology
|
| IF |
9.412
|
| リソース情報 |
| メダカ |
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