Details

Autor(en) / Beteiligte

• Bugg, Darrian
• Bailey, Logan R.J.
• Bretherton, Ross C.
• Beach, Kylie E.
• Reichardt, Isabella M.
• Robeson, Kalen Z.
• Reese, Anna C.
• Gunaje, Jagadambika
• Flint, Galina
• DeForest, Cole A.
• Stempien-Otero, April
• Davis, Jennifer

Titel

MBNL1 drives dynamic transitions between fibroblasts and myofibroblasts in cardiac wound healing

Ist Teil von

• Cell stem cell, 2022-03, Vol.29 (3), p.419-433.e10

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2022

Quelle

Access via ScienceDirect (Elsevier)

Beschreibungen/Notizen

• Dynamic fibroblast to myofibroblast state transitions underlie the heart’s fibrotic response. Because transcriptome maturation by muscleblind-like 1 (MBNL1) promotes differentiated cell states, this study investigated whether tactical control of MBNL1 activity could alter myofibroblast activity and fibrotic outcomes. In healthy mice, cardiac fibroblast-specific overexpression of MBNL1 transitioned the fibroblast transcriptome to that of a myofibroblast and after injury promoted myocyte remodeling and scar maturation. Both fibroblast- and myofibroblast-specific loss of MBNL1 limited scar production and stabilization, which was ascribed to negligible myofibroblast activity. The combination of MBNL1 deletion and injury caused quiescent fibroblasts to expand and adopt features of cardiac mesenchymal stem cells, whereas transgenic MBNL1 expression blocked fibroblast proliferation and drove the population into a mature myofibroblast state. These data suggest MBNL1 is a post-transcriptional switch, controlling fibroblast state plasticity during cardiac wound healing. [Display omitted] •MBNL1 regulation of cardiac fibroblast fate modulates scar formation and maturation•MBNL1 regulates MI-induced cardiac fibroblast proliferation•MBNL1 is necessary and sufficient to induce and maintain mature myofibroblast states•MBNL1 stabilizes transcripts that underlie profibrotic fibroblast states Bugg and colleagues demonstrate that following myocardial infarction, MBNL1 expression regulates cardiac fibroblast proliferation as well as the transition to and maintenance of an activated myofibroblastic state, which is associated with altered production and maturation of fibrotic scarring and cardiac muscle remodeling.