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Myofibroblasts from diverse pathologic settings are heterogeneous in their content of actin isoforms and intermediate
O Skalli1, W Schürch, T Seemayer
1Department of Pathology, University of Geneva, Switzerland.
Abstract:
We examined by immunofluorescence the distribution of vimentin, desmin, alpha-smooth muscle actin and alpha-sarcomeric actin in normal human soft tissues and in pathologic tissues containing myofibroblasts, including normally healing granulation tissue, hypertrophic scar, and fibromatosis. The pattern of actin isoforms was also documented biochemically by two-dimensional gel electrophoresis. Fibroblastic and/or myofibroblastic cells in each setting always expressed vimentin and never alpha-sarcomeric actin. Moreover, these cells showed an heterogeneous cytoskeletal composition which defined four phenotypes: (a) cells expressing only vimentin; (b) cells expressing vimentin, alpha-smooth muscle actin and desmin; (c) cells expressing vimentin and alpha-smooth muscle actin; and (d) cells expressing vimentin and desmin. Given this, two groups of lesions are distinguished: the first contains only vimentin cells and consists of normally healing granulation tissue, eschars and normally healed scars; the second contains vimentin cells admixed with variable proportions of vimentin, alpha-smooth muscle actin and desmin, vimentin and alpha-smooth muscle actin, and vimentin and desmin cells and consists of hypertrophic scars and fibromatoses. Immunogold electron microscopy showed that alpha-smooth muscle actin was present in a proportion of cells with ultrastructural features of myofibroblasts. Our findings suggest that contrary to myofibroblasts of normally healing granulation tissue and normally healed scars, myofibroblasts of pathologic conditions characterized by chronic retraction express always immunochemical features indicative of smooth muscle differentiation.
Insights
Myofibroblasts in normal healing tissues differ from those in chronic retraction conditions. Pathologic myofibroblasts show smooth muscle differentiation, unlike those in normal healing or scars.
Area of Science:
- Cell Biology
- Tissue Repair
- Pathology
Background:
- Myofibroblasts are key cells in wound healing and fibrosis.
- Their cytoskeletal composition, particularly actin isoforms, is crucial for their function.
- Understanding myofibroblast heterogeneity is important for studying tissue repair and pathology.
Purpose of the Study:
- To investigate the distribution and expression of actin isoforms in myofibroblasts.
- To differentiate myofibroblast phenotypes in normal healing versus pathologic conditions.
- To identify markers of smooth muscle differentiation in myofibroblasts associated with chronic retraction.
Main Methods:
- Immunofluorescence staining for vimentin, desmin, alpha-smooth muscle actin, and alpha-sarcomeric actin.
- Biochemical analysis using two-dimensional gel electrophoresis.
- Immunogold electron microscopy to examine ultrastructural features.
Main Results:
- Fibroblastic/myofibroblastic cells consistently expressed vimentin and lacked alpha-sarcomeric actin.
- Four distinct cytoskeletal phenotypes were identified based on actin and desmin expression.
- Normal healing tissues contained only vimentin-expressing cells, while hypertrophic scars and fibromatoses showed mixed phenotypes, including smooth muscle actin and desmin.
- Alpha-smooth muscle actin was found in myofibroblasts with features of smooth muscle differentiation in pathologic tissues.
Conclusions:
- Myofibroblasts in normal healing and scars exhibit distinct cytoskeletal profiles compared to those in chronic retraction pathologies.
- Pathologic myofibroblasts in conditions like hypertrophic scars and fibromatoses display immunochemical evidence of smooth muscle differentiation.
- These findings highlight the heterogeneity of myofibroblasts and their specialized roles in different tissue contexts.