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Query: UNIPROT:P06889 (Mol)
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The developmentally regulated expression of fibronectin (FN) in developing organs and FN's ability to stimulate cell migration and differentiation in vitro suggest a role in organogenesis. We examined the distribution of FN and the alpha 5 subunit of its receptor, the integrin alpha 5 beta 1, in the lungs and hearts of murine embryos at 11, 13, 16, and 18 days of gestation. In the lung, FN staining was present in the mesenchyme and parabronchial cells at day 11, increased at day 13, and decreased after day 16. Increases in FN coincided with the period of branching morphogenesis, and FN was concentrated at areas of airway bifurcation, suggesting a role for FN in cleft formation. The alpha 5 subunit appeared later at 13 days, co-distributing with FN only in well-developed primary bronchioles. At all stages, alpha-smooth muscle actin expression correlated temporally and spatially with that of the alpha 5 subunit. In the heart, staining for FN, the alpha 5 subunit, and alpha-smooth muscle actin were present at day 11 and increased at day 13. FN was present in the outflow tract and developing atria and ventricles, where it was concentrated in the outer layer or visceral pericardium. Interestingly, alpha 5 was detected at the inner layer, the endothelium, lining the outflow tract and atrioventricular cushions where endothelial cells migrate into the cardiac jelly in the process of epithelial-mesenchymal transformation. This suggests a potential role for alpha 5 beta 1 and FN in ventricular septation and valve formation.(ABSTRACT TRUNCATED AT 250 WORDS)
Am J Respir Cell Mol Biol 1992 May
PMID:Expression of fibronectin, the integrin alpha 5, and alpha-smooth muscle actin in heart and lung development. 153 75

The cellular origin of estrogen-induced kidney tumors in male Syrian hamsters has been repeatedly the subject of controversy. Several authors have proposed that the tumors arise from proximal tubules, from a combination of tubular and interstitial stromal cells, or solely from interstitial cells. Because of the model character of this tumor for hormone-associated cancer, it was further investigated in this study with respect to morphology, enzyme and intermediate filament pattern, the expression of alpha-smooth muscle actin and the extracellular matrix proteins fibronectin and tenascin. These analyses were carried out with early and late tumors as well as metastases to determine possible changes in expression of biochemical parameters during the development and progression of this neoplasm. The enzyme histochemical and intermediate filament patterns were usually the same as those described previously for proliferative foci and early tumors, i.e. highly elevated activities of glucose-6-phosphate dehydrogenase, adenylate cyclase and alkaline phosphatase, a lack of glucose-6-phosphatase and gamma-glutamyltransferase and coexpression of vimentin and desmin, alpha-smooth muscle actin could not be detected in early lesions. In five of 24 advanced tumors inclusions of kidney tubules were found which showed various degrees of alteration in their morphology and enzyme histochemical pattern, but were often directly connected with tubular segments of normal appearance outside the tumor. Like the normal tubules, the enclosed tubular segments were strongly positive for cytokeratin but never expressed vimentin or desmin. Among the 24 tumors studied, two contained cysts which expressed cytokeratin and sometimes also vimentin but not desmin. The enzyme histochemistry of the cells lining the cysts was similar to that of the surrounding tumor mass, except adenylate cyclase was lacking and alkaline phosphatase was not uniformly distributed. In tumors containing cytokeratin-positive cysts, there often were cytokeratin-positive, vimentin-negative and desmin-negative tumor formations in close contact to these cysts. With the exception of cyst formation, the pattern of metastases were identical to that of the primary tumors. All large tumors and the main component of the metastases expressed vimentin, desmin and fibronectin. Mesothelia surrounding metastatic tumor complexes were positive for vimentin, desmin, alpha-smooth muscle actin, fibronectin, cytokeratin and tenascin. It was concluded from these and previous observations on early stages of tumor development that the estrogen-induced hamster kidney tumor originates from mesenchymal interstitial cells (probably pericytes) which may rarely acquire an epithelial phenotype by metaplastic transformation during tumor progression.
Virchows Arch B Cell Pathol Incl Mol Pathol 1991
PMID:Changes in the cellular phenotype and extracellular matrix during progression of estrogen-induced mesenchymal kidney tumors in Syrian hamsters. 171 81

Endothelin, synthesized by endothelial cells, is the most potent vasoconstrictor and bronchoconstrictor agent known. We investigated endothelin release from human bronchial epithelial cells and the binding of the peptide to autologous bronchial smooth muscle cells in culture. Epithelial and smooth muscle cells were isolated by enzymatic digestion of bronchial tissue obtained on surgery, and cultured to confluency by standard methods. Epithelial cells stained positively for cytokeratin filaments. Smooth muscle cells stained uniformly for alpha-smooth muscle actin. Immunoreactive endothelin contents in the supernatants of epithelial cells extracted on C8 Amprep columns were evaluated by radioimmunoassay. Epithelial cells released appreciable amounts of immunoreactive endothelin into the culture medium (from 0.65 to 2.1 pmol/ml). A single specific binding site for [125I]endothelin 1 was identified on bronchial smooth muscle cells with an apparent Kd of 113 pM and a maximal binding capacity of 22.1 fmol/10(6) cells. At room temperature the binding was saturable, reached equilibrium at 120 min (25 pM endothelin 1), and was slowly and incompletely reversed by unlabeled endothelin over a period of 8 h. Conditioned medium from epithelial cells inhibited the [125I]endothelin 1 binding, dose dependently, and the effect was antagonized by monospecific antiserum. Thus, human bronchial smooth muscle cells possess specific binding sites for endothelin 1 and human bronchial epithelial cells secrete an endothelin-like material. This may have a role in the pathogenesis of asthma.
Am J Respir Cell Mol Biol 1990 Aug
PMID:Specific binding of endothelin on human bronchial smooth muscle cells in culture and secretion of endothelin-like material from bronchial epithelial cells. 219 95

A thickened bronchial epithelial basement membrane has long been regarded as a histopathologic characteristic of bronchial asthma. As we had previously demonstrated that this phenomenon is due to the deposition of interstitial collagens and fibronectin, we have now sought to determine the nature of the cell responsible for this process by studying endobronchial biopsies from eight normal and seven asthmatic volunteers by immunohistochemistry and electron microscopy. Biopsies were stained with PR 2D3, a monoclonal antibody to myofibroblasts of the pericrypt sheath of the colon and a monoclonal antibody to alpha-smooth muscle actin. The thickness of the subepithelial collagen and the organelle content of the cells therein were determined by electron microscopy. The subepithelial collagen thickness in the normal subjects ranged from 2.16 to 6.26 microns, while that in the asthmatic subjects ranged from 3.75 to 11.1 microns (Mann-Whitney test; P = 0.05). Elongated cells in the collagen layer were identified by staining with PR 2D3. As this antibody also stains smooth muscle, consecutive frozen sections were stained for alpha-smooth muscle actin and the number of positive cells per millimeter of basement membrane was subtracted from the count for PR 2D3. This yielded a count of 4.9 to 9.4 cells/mm in the normal subjects and 11.9 to 20.6 cells/mm in the asthmatics (P = 0.001). There was a highly significant correlation between the depth of subepithelial collagen and the number of PR 2D3-positive, alpha-smooth muscle actin-positive cells (Spearman rank correlation; r = 0.764 and P = 0.006). Electron microscopy confirmed the myofibroblastic nature of these cells.(ABSTRACT TRUNCATED AT 250 WORDS)
Am J Respir Cell Mol Biol 1990 Nov
PMID:Myofibroblasts and subepithelial fibrosis in bronchial asthma. 222 5

We employed a panel of antibodies directed against cytoskeletal and contractile proteins in a developmental study to follow the differentiation and distribution of smooth muscle-like cells in the rat lung. We observed that, in the mesenchyme around developing airways and vessels, desmin replaces vimentin as the predominant intermediate filament as specialization toward smooth muscle occurs. Normally, desmin and smooth muscle myosin were expressed together in the cells and their acquisition appeared indicative of terminal differentiation of smooth muscle. In this regard, the maturation of vascular smooth muscle is delayed in the lung relative to that surrounding the developing air passages. alpha-smooth muscle actin-containing cells form a thicker coat around the primitive airway tubes and extend farther down the tree than desmin or smooth muscle myosin-positive cells. This suggests that the alpha-actin is a marker for initial differentiation of smooth muscle cells and that these cells arise from the enveloping mesenchyme. In the pseudoglandular and canalicular lung, alpha-actin-containing cells were also found in regions of epithelial tube cleft formation, suggesting an association with the process of branching morphogenesis. In addition, a large complement of alpha-actin-positive but smooth muscle myosin-negative cells were observed in the saccular interstitium during the period of secondary saccule formation and capillary reorganization that leads to final alveolarization. In summary, we note an association of smooth muscle-like, alpha-actin-containing cells with areas and periods of remodeling during normal pulmonary development. This observation may have relevance to the repair process in the adult lung.
Am J Respir Cell Mol Biol 1990 Dec
PMID:Smooth muscle cell markers in developing rat lung. 225 78

An immunohistochemical investigation of alpha-smooth muscle actin (alpha-SM actin) using the monoclonal anti-alpha-SM-1 antibody was carried out in 15 normal ovaries, in three ovaries with stromal hyperplasia and in 27 neoplastic ovaries. In selected cases the pattern of actin isoforms was examined by means of 2 D-gel electrophoresis. In addition, the tissues were stained for vimentin and desmin. In normal ovaries alpha-SM actin was found in the inner cortex and in the theca externa. In ovarian stromal hyperplasia expression of alpha-SM actin was minimal or absent. In primary and metastatic epithelial tumors there was positive stromal staining for alpha-SM actin, especially in the vicinity of epithelial elements. This tended to be more widespread in malignant neoplasms. Thecomas did not express alpha-SM-actin and could thus be differentiated from leiomyomas which stained intensely for alpha-SM actin. Only focal stromal staining of alpha-SM actin was observed in granulosa and germ cell tumors. In all the tissues studied blood vessels were strongly positive for alpha-SM actin. Desmin, although present in the stroma of most of the specimens, was less abundant than alpha-SM actin. We concluded that alpha-SM actin is a component of the normal human ovary where it may contribute to the contractility of its stroma. Its absence in the normal outer cortex and theca interna, and in stromal hyperplasia and thecoma implies that sex hormones do not constitute a stimulus for alpha-SM actin production in the ovary. Among neoplasms it is most widely represented in the stroma of epithelial tumors in which it may reflect stromal stimulation mediated by neoplastic epithelium.
Virchows Arch B Cell Pathol Incl Mol Pathol 1989
PMID:Alpha smooth muscle actin (alpha-SM actin) in normal human ovaries, in ovarian stromal hyperplasia and in ovarian neoplasms. 256 50

A series of 217 trephine bone marrow biopsies from adult patients and specimens from 16 fetuses and 5 infants were examined for the presence of stromal myoid cells (MCs) using a monoclonal antibody recognizing alpha-smooth muscle actin. In the normal adult bone marrow, stromal cells did not contain alpha-smooth muscle actin, whereas during fetal life, many alpha-smooth muscle actin-containing MCs were connected with vascular sinusoids in the primitive bone marrow. This cell type reappeared in various characteristic distribution patterns in adult bone marrow during different neoplastic and non-neoplastic conditions including metastatic carcinoma, Hodgkin's disease, multiple myeloma, hairy cell leukemia, acute myeloid leukemia (FAB M4, 5, 7) and chronic myelo-proliferative diseases. In general, the appearance of MCs was associated with a slight to pronounced increase in the deposition of reticulin and collagen fibers. We propose that bone marrow MCs represent a distinct subpopulation of fiber-associated or adventitial reticular cells undergoing cytoskeletal remodeling in response to various stimuli.
Virchows Arch B Cell Pathol Incl Mol Pathol 1989
PMID:Alpha-smooth muscle actin is expressed in a subset of bone marrow stromal cells in normal and pathological conditions. 257 Apr 90

A series of 5' deletion mutations of the upstream flanking sequences of the chicken alpha-smooth muscle (aortic) actin gene was prepared and inserted into the chloramphenicol acetyltransferase expression vector pSV0CAT. Deletion recombinants were transfected into fibroblasts, which actively express the alpha-smooth muscle actin gene, and primary myoblast cultures, which accumulate much lower quantities of alpha-smooth muscle actin mRNAs. The first 122 nucleotides of 5'-flanking DNA were found to contain a "core" promoter capable of accurately directing high levels of transcription in both fibroblasts and myotubes. The activity of this core promoter is modulated in fibroblasts by a "governor" element(s) located at least in part between nucleotides -257 and -123. This region contains sequences potentially conserved between mammalian and avian alpha-smooth muscle actin genes as well as one of a pair of 16-base-pair inverted CCAAT box-associated repeats which are conserved among all chordate muscle actin genes examined to date. A smaller DNA segment (-151 to -123) containing these upstream CCAAT box-associated repeats was sufficient to suppress expression of the core promoter in muscle cultures, suggesting that the upstream CCAAT box-associated repeats play a negative role in the alpha-smooth muscle actin gene promoter.
Mol Cell Biol 1988 Jan
PMID:A 29-nucleotide DNA segment containing an evolutionarily conserved motif is required in cis for cell-type-restricted repression of the chicken alpha-smooth muscle actin gene core promoter. 333 59

Genes representing six different actin isoforms were isolated from a chicken genomic library. Cloned actin cDNAs as well as tissue-specific mRNAs enriched in different actin species were used as hybridization probes to group individual actin genomic clones by their relative thermal stability. Restriction maps showed that these actin genes were derived from separate and nonoverlapping regions of genomic DNA. Of the six isolated genes, five included sequences from both the 5' and 3' ends of the actin-coding area. Amino acid sequence analysis from both the NH2- and COOH-terminal regions provided for the unequivocal identification of these genes. The striated isoforms were represented by the isolated alpha-skeletal, alpha-cardiac, and alpha-smooth muscle actin genes. The nonmuscle isoforms included the beta-cytoplasmic actin gene and an actin gene fragment which lacked the 5' coding and flanking sequence; presumably, this region of DNA was removed from this gene during construction of the genomic library. Unexpectedly, a third nonmuscle chicken actin gene was found which resembled the amphibian type 5 actin isoform (J. Vandekerckhove, W. W. Franke, and K. Weber, J. Mol. Biol., 152:413-426). This nonmuscle actin type has not been previously detected in warm-blooded vertebrates. We showed that interspersed, repeated DNA sequences closely flanked the alpha-skeletal, alpha-cardiac, beta-, and type 5-like actin genes. The repeated DNA sequences which surround the alpha-skeletal actin-coding regions were not related to repetitious DNA located on the other actin genes. Analysis of genomic DNA blots showed that the chicken actin multigene family was represented by 8 to 10 separate coding loci. The six isolated actin genes corresponded to 7 of 11 genomic EcoRI fragments. Only the alpha-smooth muscle actin gene was shown to be split by an EcoRI site. Thus, in the chicken genome each actin isoform appeared to be encoded by a single gene.
Mol Cell Biol 1984 Nov
PMID:Isolation and characterization of six different chicken actin genes. 651 27

Morphologic changes are reported to occur in rat lung vasculature after 3 days of hypoxia. We have previously shown that immunoreactivity for the vasodilator calcitonin gene-related peptide (CGRP) is increased in pulmonary endocrine cells by 7 days of hypoxia. Because these cells may be among the earliest mediators of the hypoxic response, we examined endocrine cell CGRP content in rat lung after 0, 2, 4, and 8 h and 1, 5, 10, 15, 20, 28, and 35 days of normobaric hypoxia, using optimal and supraoptimal dilutions of CGRP antibodies to demonstrate changes in CGRP immunoreactivity. This was compared with temporal changes in pulmonary vascular smooth muscle after 1, 5, and 20 days of hypoxia exposure by evaluating vascular immunoreactivity for alpha-smooth muscle actin (alpha-SM actin), platelet-derived growth factor (PDGF) beta-receptor, and proliferating cell nuclear antigen (PCNA). Significant increases in endocrine cell CGRP immunoreactivity were found after 4 h of hypoxia, and levels increased up to 1 day, followed by a decrease (at 5 days) and then a progressive increase up to 35 days. After 1 day of hypoxia, the number of vessels displaying immunoreactivity for alpha-SM actin, PDGF beta-receptor, and PCNA were also significantly increased. Whereas PDGF beta-receptor and PCNA returned to control values by day 20, alpha-SM actin reached a plateau that persisted until 20 days. The results indicate that modulation of endocrine cell CGRP content in response to hypoxia is rapid and characterized by a significant and persistent increase, paralleled by a proliferation of vascular cells leading to vascular muscularization.(ABSTRACT TRUNCATED AT 250 WORDS)
Am J Respir Cell Mol Biol 1993 Nov
PMID:Early changes in the calcitonin gene-related peptide (CGRP) content of pulmonary endocrine cells concomitant with vascular remodeling in the hypoxic rat. 810 30


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