Correlation between the distribution of smooth muscle or non muscle myosins and α‐smooth muscle actin in normal and pathological soft tissues

Benzonana, Gilbert; Skalli, Omar; Gabbiani, Giulio

doi:10.1002/cm.970110405

Cited by 95 publications

(43 citation statements)

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“…TGF-,6 is synthesized in a latent form and is often immobilized in the extracellular matrix (54,55). In either case, however, this growth factor would Myofibroblast Origin in Breast Cancer 867 (60), or to appear in 10-15% of the entire cell populations (15,44).…”

Section: Discussionmentioning

confidence: 99%

The origin of the myofibroblasts in breast cancer. Recapitulation of tumor environment in culture unravels diversity and implicates converted fibroblasts and recruited smooth muscle cells.

Rønnov‐Jessen¹,

Petersen²,

Koteliansky³

et al. 1995

J. Clin. Invest.

377

287

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The origin of myofibroblasts in stromal reaction has been a subject of controversy. To address this question definitively, we developed techniques for purification and characterization of major stromal cell types. We defined a panel of markers that could, in combination, unequivocally distinguish these cell types by immunocytochemistry, iso-electric focusing, immunoblotting, and two-dimensional gel electrophoresis. We then devised an assay to recapitulate in culture, within two weeks of incubation, critical aspects of the microenvironment in vivo including the typical tissue histology and stromal reaction. When confronted with tumor cells in this assay, fibroblasts readily converted into a graded pattern of myogenic differentiation, strongest in the immediate vicinity of tumor cells. Vascular smooth muscle cells (VSMC), in contrast, did not change appreciably and remained coordinately smooth muscle differentiated. Midcapillary pericytes showed only a slight propensity for myogenic differentiation. Analysis of ten primary tumors implicated converted fibroblasts (10/10), vascular smooth muscle cells (4/10), and pericytes (1/10) in the stromal reaction. Tumor cells were shown to specifically denude the venules both in culture and in vivo, explaining the VSMC phenotype in the stroma. The establishment of this assay and clarification of the origin of these cells pave the way for further analysis of the mechanisms of conversion, and of the consequence of such heterogeneity for diagnosis and treatment. (J. Clin. Invest. 1995. 95:859-873.)

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Section: Discussionmentioning

confidence: 99%

The origin of the myofibroblasts in breast cancer. Recapitulation of tumor environment in culture unravels diversity and implicates converted fibroblasts and recruited smooth muscle cells.

Rønnov‐Jessen¹,

Petersen²,

Koteliansky³

et al. 1995

J. Clin. Invest.

377

287

View full text Add to dashboard Cite

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“…12, September 2001Cells were stained for ␣-SMA (anti-␣SM-1, IgG2a mAb; Skalli et al, 1986), F-actin (Phalloidin-Alexa 488, Molecular Probe, Eugene, OR), ␤-cytoplasmic (␤74, rbAb; Yao et al, 1995), ␣-sarcomeric actin (SR-1, IgM mAb; Dako), ␥-actins and ␣-SMA (AAL-20, rbAb), ED-A FN (IST-9, IgG1 mAb, gift from Dr. L. Zardi, National Institute for Cancer Research, Laboratory of Cell Biology, Genoa, Italy; Carnemolla et al, 1987), VSV-G-tag (anti-VSV-G-tag, rbAB, a gift of Dr. J.-C. Perriard, ETH, Zü rich, CH), the heavy chains (HC) of SMM and NMM (anti-SMMHC and anti-NMMHC, rbAbs; Benzonana et al, 1988) and DNA (DAPI). As secondary antibodies TRITC-and FITC-conjugated goat anti-mouse subclasses IgG1 and IgG2a (Southern Biotechnology Associates Inc., Birmingham, AL), IgG, IgM, and goat anti-rabbit antibodies (Jackson ImmunoResearch Laboratories, West Grove, PA) were used.…”

Section: Fibroblast Contractionmentioning

confidence: 99%

Alpha-Smooth Muscle Actin Expression Upregulates Fibroblast Contractile Activity

Hinz

Celetta

Tomasek³

et al. 2001

MBoC

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1,096

947

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To evaluate whether ␣-smooth muscle actin (␣-SMA) plays a role in fibroblast contractility, we first compared the contractile activity of rat subcutaneous fibroblasts (SCFs), expressing low levels of ␣-SMA, with that of lung fibroblasts (LFs), expressing high levels of ␣-SMA, with the use of silicone substrates of different stiffness degrees. On medium stiffness substrates the percentage of cells producing wrinkles was similar to that of ␣-SMA-positive cells in each fibroblast population. On high stiffness substrates, wrinkle production was limited to a subpopulation of LFs very positive for ␣-SMA. In a second approach, we measured the isotonic contraction of SCF-and LF-populated attached collagen lattices. SCFs exhibited 41% diameter reduction compared with 63% by LFs. TGF␤1 increased ␣-SMA expression and lattice contraction by SCFs to the levels of LFs; TGF␤-antagonizing agents reduced ␣-SMA expression and lattice contraction by LFs to the level of SCFs. Finally, 3T3 fibroblasts transiently or permanently transfected with ␣-SMA cDNA exhibited a significantly higher lattice contraction compared with wild-type 3T3 fibroblasts or to fibroblasts transfected with ␣-cardiac and ␤-or ␥-cytoplasmic actin. This took place in the absence of any change in smooth muscle or nonmuscle myosin heavy-chain expression. Our results indicate that an increased ␣-SMA expression is sufficient to enhance fibroblast contractile activity. INTRODUCTIONEarly during healing of an open wound, resident dermal fibroblasts proliferate from the wound margin and migrate into the provisional matrix composed of a fibrin clot. About 1 week after wounding, the provisional matrix is replaced by neo-formed connective tissue, known as granulation tissue, essentially composed of small vessels, extracellular matrix, and fibroblastic cells that become activated and modulate into myofibroblasts. The main feature of myofibroblasts is represented by an important contractile apparatus similar to that of smooth muscle (Gabbiani et al., 1971), and in particular by the neo-expression of ␣-smooth muscle actin (␣-SMA), the actin isoform typical of vascular smooth muscle cells (Skalli et al., 1986). Myofibroblasts are recognized to play a central role in closing the wound tissue, through their capacity to produce a strong contractile force (for review see Grinnell, 1994;Rønnov-Jessen et al., 1996;Powell et al., 1999;Serini and Gabbiani, 1999), possibly generated within stress fibers, similar to those present in cultured fibroblasts (Skalli et al., 1986;Serini and Gabbiani, 1999). Because wound contraction takes place when de novo expressed ␣-SMA is incorporated in stress fibers (Darby et al., 1990), it has been suggested that this actin isoform plays an important role in granulation tissue contraction (for review see Serini and Gabbiani, 1999). Although stress fibers have been proposed to function as contractile organelles (Burridge, 1981;Katoh et al., 1998) and their presence has been correlated with the production of isometric tension (Harris et al., 1981), at p...

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“…We used an affinity-purified rabbit polyclonal immunoglobulin (IgG) that recognizes only MYH9 (NMMHC-A) and MYH10 (NMMHC-B) 29 (Biomedical Technologies, Stoughton, MA). This step was followed by a TRITC (tetramethylrhodamine-B-isothiocyanate)-conjugated swine antirabbit IgG (Dako, Glostrup, Denmark).The secondary antibody alone was used as a negative control.…”

Section: Immunohistochemistrymentioning

confidence: 99%

Asp1424Asn MYH9 mutation results in an unstable protein responsible for the phenotypes in May-Hegglin anomaly/Fechtner syndrome

Deutsch

Rideau

Bochaton-Piallat

et al. 2003

Blood

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IntroductionFamilial macrothrombocytopenias with leukocyte inclusion bodies are a group of rare autosomal dominant disorders characterized by mild bleeding symptoms, giant platelets, and Döhle-like inclusion bodies in peripheral blood granulocytes. These disorders, which include the May-Hegglin anomaly (MHA; OMIM [Online Mendelian Inheritance in Man], #155100), Sebastian syndrome (SBS; OMIM, #605249), Fechtner syndrome (FTNS; OMIM, #153640), and Epstein syndrome (EPS; OMIM, #153650) all have largely overlapping phenotypes but were previously considered as separate clinical entities. [1][2][3][4] Biochemical analysis of platelets from patients with MHA revealed no abnormalities in the function of these cells, 5,6 leading to the hypothesis that the hematologic phenotype in patients may result from a deficit in the demarcation membranes in megakaryocytes prior to platelet formation. 7 MHA and SBS are distinguished from each other by small differences in their inclusion bodies revealed by electron microscopy examination. 8 FTNS and EPS, however, manifest a number of nonhematologic traits similar to those observed in Alport syndrome cases, such as nephritis, high-tone sensorineural deafness, and bilateral cataracts, all of which are present with variable expressivity. 1,9,10 The discovery that the genetic loci for all of these syndromes mapped to chromosome 22q12.3 Ϫq13.2, 11-13 and the identification of mutations in the MYH9 gene for each of them, showed that this group of pathologies represent allelic variations of a single genetic disorder. [14][15][16][17][18] MYH9, a 5.8-kb (kilobase) mRNA transcript, encodes for the nonmuscle myosin heavy chain A (also known as NMMHC-A), a large cytoplasmic protein that forms part of the myosin II hexameric complex. 19,20 MYH9 consists of an adenosine triphosphatase (ATPase) globular head domain at its N-terminus and a C-terminal tail domain that forms a coiled coil structure on dimerization.The function of nonmuscular myosin II (MYH9 containing) has not been fully characterized. 21 It has been shown to form clusters of minifilaments in the cytoplasm, which concentrate in stress fibers near the periphery of cells and in the cleavage furrow of dividing cells. 22 Nonmuscular myosin is involved in processes such as phagocytosis 23 and cytokinesis, and in the latter it is thought to drive constriction of the cleavage furrow, as shown elegantly in Dictyostelium discoideum, where myosin IInull cells fail to divide. 24 These data are consistent with the originally proposed disease mechanism of impaired thrombopoiesis as a result of defects in cytoskeleton rearrangement in megakaryocytes, 7 although this is still a poorly understood process.The MYH9 gene has subsequently been found to be involved in 2 further disorders, DFNA17 (OMIM, #603622), an autosomal 25 and APSM (OMIM, #153650), a variant of Alport syndrome with macrothrombocytopenia. 16 To date, 20 different disease-associated mutations have been found in the MYH9 gene, covering the range of phenotypes represented by the 6 clin...

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Correlation between the distribution of smooth muscle or non muscle myosins and α‐smooth muscle actin in normal and pathological soft tissues

Cited by 95 publications

References 50 publications

The origin of the myofibroblasts in breast cancer. Recapitulation of tumor environment in culture unravels diversity and implicates converted fibroblasts and recruited smooth muscle cells.

The origin of the myofibroblasts in breast cancer. Recapitulation of tumor environment in culture unravels diversity and implicates converted fibroblasts and recruited smooth muscle cells.

Alpha-Smooth Muscle Actin Expression Upregulates Fibroblast Contractile Activity

Asp1424Asn MYH9 mutation results in an unstable protein responsible for the phenotypes in May-Hegglin anomaly/Fechtner syndrome

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