The role of immunohistochemistry for smooth-muscle actin, p63, CD10 and cytokeratin 14 in the differential diagnosis of papillary lesions of the breast

In bronchopulmonary dysplasia (BPD), alveolar septa are thickened with collagen and α-smooth muscle actin-, transforming growth factor (TGF)-β-positive myofibroblasts. We examined the biochemical mechanisms underlying myofibroblastic differentiation, focusing on the role of glycogen synthase kinase-3β (GSK-3β)/β-catenin signaling pathway. In the cytoplasm, β-catenin is phosphorylated on the NH2 terminus by constitutively active GSK-3β, favoring its degradation. Upon TGF-β stimulation, GSK-3β is phosphorylated and inactivated, allowing β-catenin to translocate to the nucleus, where it activates transcription of genes involved in myofibroblastic differentiation. We examined the role of β-catenin in TGF-β1-induced myofibroblastic differentiation of neonatal lung mesenchymal stromal cells (MSCs) isolated from tracheal aspirates of premature infants with respiratory distress. TGF-β1 increased β-catenin expression and nuclear translocation. Transduction of cells with GSK-3β S9A, a nonphosphorylatable, constitutively active mutant that favors β-catenin degradation, blocked TGF-β1-induced myofibroblastic differentiation. Furthermore, transduction of MSCs with ΔN-catenin, a truncation mutant that cannot be phosphorylated on the NH2 terminus by GSK-3β and is not degraded, was sufficient for myofibroblastic differentiation. In vivo, hyperoxic exposure of neonatal mice increases expression of β-catenin in α-smooth muscle actin-positive myofibroblasts. Similar changes were found in lungs of infants with BPD. Finally, low-passage unstimulated MSCs from infants developing BPD showed higher phospho-GSK-3β, β-catenin, and α-actin content compared with MSCs from infants not developing this disease, and phospho-GSK-3β and β-catenin each correlated with α-actin content. We conclude that phospho-GSK-3β/β-catenin signaling regulates α-smooth muscle actin expression, a marker of myofibroblast differentiation, in vitro and in vivo. This pathway appears to be activated in lung mesenchymal cells from patients with BPD.

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Multiple Myeloma-Derived Exosomes Regulate the Functions of Mesenchymal Stem Cells Partially via Modulating miR-21 and miR-146a

Stem Cells International ◽

10.1155/2017/9012152 ◽

2017 ◽

Vol 2017 ◽

pp. 1-9 ◽

Cited By ~ 22

Author(s):

Qian Cheng ◽

Xin Li ◽

Jingru Liu ◽

Qinmao Ye ◽

Yanfang Chen ◽

...

Keyword(s):

Stem Cells ◽

Multiple Myeloma ◽

Mesenchymal Stem Cells ◽

Smooth Muscle ◽

Cancer Cells ◽

Smooth Muscle Actin ◽

Muscle Actin ◽

Cancer Associated Fibroblast ◽

Secretion Inhibition

Exosomes derived from cancer cells can affect various functions of mesenchymal stem cells (MSCs) via conveying microRNAs (miRs). miR-21 and miR-146a have been demonstrated to regulate MSC proliferation and transformation. Interleukin-6 (IL-6) secreted from transformed MSCs in turn favors the survival of multiple myeloma (MM) cells. However, the effects of MM exosomes on MSC functions remain largely unclear. In this study, we investigated the effects of OPM2 (a MM cell line) exosomes (OPM2-exo) on regulating the proliferation, cancer-associated fibroblast (CAF) transformation, and IL-6 secretion of MSCs and determined the role of miR-21 and miR-146a in these effects. We found that OPM2-exo harbored high levels of miR-21 and miR-146a and that OPM2-exo coculture significantly increased MSC proliferation with upregulation of miR-21 and miR-146a. Moreover, OPM2-exo induced CAF transformation of MSCs, which was evidenced by increased fibroblast-activated protein (FAP), α-smooth muscle actin (α-SMA), and stromal-derived factor 1 (SDF-1) expressions and IL-6 secretion. Inhibition of miR-21 or miR-146a reduced these effects of OPM2-exo on MSCs. In conclusion, MM could promote the proliferation, CAF transformation, and IL-6 secretion of MSCs partially through regulating miR21 and miR146a.

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Morphological changes of rat atrial cardiomyocytes contractile apparatus in normal conditions and under the influence of acute and chronic prenatal hypoxia. Role of α-smooth muscle actin in myofibrilogenesis.

Morphologia ◽

10.26641/1997-9665.2016.2.85-92 ◽

2016 ◽

Vol 10 (2) ◽

pp. 85-92

Author(s):

K. M. Shevchenko

Keyword(s):

Smooth Muscle ◽

Morphological Changes ◽

Smooth Muscle Actin ◽

Prenatal Hypoxia ◽

Muscle Actin ◽

Contractile Apparatus ◽

Atrial Cardiomyocytes

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Alpha Smooth Muscle Actin (αSMA) Immunohistochemistry Use in the Differentiation of Pancreatic Cancer from Chronic Pancreatitis

Journal of Clinical Medicine ◽

10.3390/jcm10245804 ◽

2021 ◽

Vol 10 (24) ◽

pp. 5804

Author(s):

Katarzyna Winter ◽

Monika Dzieniecka ◽

Janusz Strzelczyk ◽

Małgorzata Wągrowska-Danilewicz ◽

Marian Danilewicz ◽

...

Keyword(s):

Pancreatic Cancer ◽

Smooth Muscle ◽

Chronic Pancreatitis ◽

Smooth Muscle Actin ◽

Healthy Tissue ◽

Pancreatic Stellate Cells ◽

Resected Specimen ◽

Muscle Actin ◽

Alpha Smooth Muscle Actin

Aim: Fibrosis is observed both in pancreatic cancer (PDAC) and chronic pancreatitis (CP). The main cells involved in fibrosis are pancreatic stellate cells (PSCs), which activate alpha smooth muscle actin (αSMA), which is considered to be the best-known fibrosis marker. The aim of the study was to evaluate the expression of the αSMA in patients with PDAC and CP as the possible differentiation marker. Methods: We enrolled 114 patients undergoing pancreatic resection: 83 with PDAC and 31 with CP. Normal fragments of resected specimen from 21 patients represented the control tissue. The immunoexpressions of αSMA were detected in tissue specimens with immunohistochemistry (Abcam antibodies, GB). Results: Mean cytoplasmatic expression of αSMA protein in PDAC stromal cells was significantly higher compared to CP: 2.42 ± 0.37 vs 1.95 ± 0.45 (p < 0.01) and control group 0.61 ± 0.45 (p < 0.01). Strong immunoexpression of the αSMA protein was found in the vast majority (80.7%) of patients with PDAC, in about half (58%) of patients with CP, and not at all in healthy tissue. The expression of αSMA of different intensity was found in all patients with PDAC and CP, while in healthy tissue was minimal or absent. In PDAC patients, αSMA expression was significantly higher in tumors of diameter higher than 3 cm compared to smaller ones (p = 0.017). Conclusions: Presented findings confirm the significant role of fibrosis in both PDAC and CP; however, they do not confirm the role of αSMA as a marker of differentiation.

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Mediatory role of interleukin-6 in α smooth muscle actin induction and myofibroblast formation around silicone tissue expander

Journal of Biomedical Materials Research Part A ◽

10.1002/jbm.a.34596 ◽

2013 ◽

Vol 101 (10) ◽

pp. 2967-2973 ◽

Cited By ~ 5

Author(s):

Josna Joseph ◽

Kumary Thrikkovil Variathu ◽

Mira Mohanty

Keyword(s):

Smooth Muscle ◽

Interleukin 6 ◽

Smooth Muscle Actin ◽

Tissue Expander ◽

Muscle Actin

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Primary leiomyoma of the thyroid gland

The Journal of Laryngology & Otology ◽

10.1258/002221503770716322 ◽

2003 ◽

Vol 117 (10) ◽

pp. 832-834 ◽

Cited By ~ 12

Author(s):

Suna Erkiliç ◽

Ahmet Erkiliç ◽

Yildirim A. Bayazit

Keyword(s):

Differential Diagnosis ◽

Smooth Muscle ◽

Immunohistochemical Staining ◽

Smooth Muscle Actin ◽

Subtotal Thyroidectomy ◽

Muscle Actin ◽

Thyroid Lobe ◽

Surgical Specimen ◽

Spindle Cells ◽

The Right

Primary thyroid leiomyomas are rare, and only four cases have been reported to date. This is a report of an additional case of primary thyroid leiomyoma in a 40-year-old male who was admitted with a painless swelling in the right thyroid lobe and underwent subtotal thyroidectomy. The surgical specimen showed a well-circumscribed, greyish-white solid nodule. Histologically, the tumour was composed of spindle cells with blunt-ended nuclei that were arranged with short intersecting bundles.Immunohistochemical staining revealed reactivity with smooth muscle actin, vimentin and desmin. Histopathologic and immunohistochemical assessments produced the diagnosis of thyroid leiomyoma.Although primary thyroid leiomyoma is rare, it should be considered in the differential diagnosis of a cold thyroid nodule.

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