Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P15088 (mast cell)
 14,925 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To examine the pathomechanism of entrapment neuropathy associated with diabetes with special emphasis on the roles of mast cells and Tenascin-C using a rat model of Streptozotocin-induced diabetes. The roles of mast cells and Tenascin-C in development of tarsal tunnel syndrome were analyzed electrophysiologically and histologically in 20 male Ws/Ws-/-rats (mast cell deficient) and 20 of their male wild type counterparts (12-16 weeks old; 250-300 g). Rats were assigned randomly to one of the following three groups; diabetic group and nondiabetic group reared in cages with a wire grid flooring; non-diabetic group in cages with sawdust covered plastic flooring. No significant role for mast cells in entrapment neuropathy was found in the rats with streptozotocin-induced diabetes. Distal latency was prolonged in diabetic rats compared with nondiabetic rats, and positively correlated with increases in blood glucose levels. Tenascin-C expression levels in the endoneurium at the tarsal tunnel in diabetic rats were found to be correlated with distal latency. The anti-alpha-smooth muscle actin (alpha-SMA) positive myofibroblast was scattered in nerve fascicles overexpressing Tenascin-C. It seems likely that Tenascin-C expressing myofibroblasts constrict axons by inducing collagen contraction of the endoneurium. Our data indicate that metabolic and phenotypic abnormalities of endoneurium and perineum lie behind the vulnerability of diabetic patients to entrapment neuropathy.
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PMID:Pathomechanism of entrapment neuropathy in diabetic and nondiabetic rats reared in wire cages. 1799 72

IgA nephropathy (IgAN) is a kidney disease with a varying renal prognosis. Recently, many studies have demonstrated that renal alpha-smooth muscle actin (alpha-SMA) and transforming growth factor (TGF-beta1) expression, as well interstitial mast cell infiltrates could represent a prognostic marker in several renal diseases. The aim of our study was to analyze the prognostic value of mast cell, TGF-beta1 and alpha-SMA expression in IgAN. A survey of the medical records and renal biopsy reports of 62 patients with a diagnosis of IgAN followed-up from 1987 to 2003 was performed. The mean follow-up time was 74.7 +/- 50.0 months. The immunohistochemical studies were performed using a monoclonal antibody anti-human mast cell tryptase, a polyclonal antibody anti-human TGF-beta1, and a monoclonal antibody anti-human alpha-SMA. An unfavorable clinical course of IgAN was related to interstitial mast cell infiltrates and alpha-SMA expression in the tubulointerstitial area. Expression of glomerular TGF-beta1 and alpha-SMA, and interstitial TGF-beta1 is not correlated with clinical course in IgAN. In conclusion, the increased number of mast cells and higher alpha-SMA expression in the tubulointerstitial area may be predictive factors for the poor prognosis of patients with IgAN.
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PMID:Mast cells, TGF-beta1 and alpha-SMA expression in IgA nephropathy. 1833 40

Asthma is a major cause of morbidity and mortality worldwide. It is characterized by airway dysfunction and inflammation. A key determinant of the asthma phenotype is infiltration of airway smooth muscle bundles by activated mast cells. We hypothesized that interactions between these cells promotes airway smooth muscle differentiation into a more contractile phenotype. In vitro coculture of human airway smooth muscle cells with beta-tryptase, or mast cells with or without IgE/anti-IgE activation, increased airway smooth muscle-derived TGF-beta1 secretion, alpha-smooth muscle actin expression and agonist-provoked contraction. This promotion to a more contractile phenotype was inhibited by both the serine protease inhibitor leupeptin and TGF-beta1 neutralization, suggesting that the observed airway smooth muscle differentiation was driven by the autocrine release of TGF-beta1 in response to activation by mast cell beta-tryptase. Importantly, in vivo we found that in bronchial mucosal biopsies from asthmatics the intensity of alpha-smooth muscle actin expression was strongly related to the number of mast cells within or adjacent to an airway smooth muscle bundle. These findings suggest that mast cell localization in the airway smooth muscle bundle promotes airway smooth muscle cell differentiation into a more contractile phenotype, thus contributing to the disordered airway physiology that characterizes asthma.
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PMID:Mast cells promote airway smooth muscle cell differentiation via autocrine up-regulation of TGF-beta 1. 1880 3

Mast cells regulate both inflammatory responses and tissue repair in human diseases but there are conflicting reports on the role of these cells in the pathogenesis of various kidney diseases. Here we measured mast cell function in unilateral ureteral obstruction, a well-characterized model of renal fibrosis, using Kit(W)/Kit(W-v) mice genetically deficient in mast cells, wild-type mice, and deficient mice reconstituted by adoptive transfer with mast cells from the wild-type animals. Mast cell-deficient mice had higher levels of renal tubular damage, more stromal fibrosis, higher numbers of infiltrating ERHR3-positive macrophages and CD3-positive T cells, and higher tissue levels of profibrotic transforming growth factor-beta1 than wild-type mice or mice reconstituted by adoptive transfer of mast cells 3 weeks after ureteral obstruction. Similarly, while wild-type and adoptively transferred mice had increased alpha-smooth muscle actin and decreased E-cadherin expression, which are indicators of epithelial-mesenchymal transition, the obstructed kidneys of the mast cell-deficient mice had significant attenuation of those indicators. Thus, our study suggests that mast cells protect the kidney against fibrosis by modulation of inflammatory cell infiltration and by transforming growth factor-beta1-driven epithelial-to-mesenchymal transitions.
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PMID:Mast cells decrease renal fibrosis in unilateral ureteral obstruction. 1924 3

The sympathetic nervous system plays an important role in wound healing, but its mechanism of action is poorly understood. The aim of this study was to investigate the effects of beta- and alpha-adrenoceptor blockade on cutaneous wound healing. Male rats were treated with propranolol (beta1- and beta2-antagonist), atenolol (beta1-antagonist), or phentolamine (alpha1- and alpha2-antagonist) dissolved in drinking water. A full-thickness excisional lesion was created and the wound area was measured. Fourteen days after wounding, lesions and adjacent skin were removed, formalin-fixed, and paraffin-embedded. Sections were stained with hematoxylin-eosin and toluidine blue, and immunostained for alpha-smooth muscle actin and proliferating cell nuclear antigen. Wound contraction was delayed in propranolol- and atenolol-treated animals but not in phentolamine-treated animals. Reepithelialization was decreased only in propranolol-treated animals. beta1- and beta2-adrenoceptor blockade delayed leukocyte migration, epidermal and connective tissue cell proliferation, myofibroblastic differentiation, and mast cell migration. The volume density of blood vessels was increased in the propranolol- and atenolol-treated animals compared with controls. The levels of matrix metalloproteases (MMP-2 and MMP-9) decreased in the propranolol- and atenolol-treated animals. alpha1- and alpha2-adrenoceptor blockade only affected leukocyte migration, epithelial and connective tissue cell proliferation, and pro-MMP-9 levels. In conclusion, beta-1 and beta-2, but not alpha-1 and alpha-2, adrenoceptor blockade delays cutaneous wound healing.
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PMID:beta-1 and beta-2, but not alpha-1 and alpha-2, adrenoceptor blockade delays rat cutaneous wound healing. 1932 Aug 92

Cigarette smoke has been associated with poor healing in several studies, but the precise mechanisms involving this impairment are still not elucidated. The aim of this work was to investigate cigarette smoke exposure effects on initial phases of cutaneous healing in mice, focusing mainly on gene expression of two molecules involved in wound repair (Ccn2/Ctgf and Tgfb1) and to study if these effects are strain dependent. Mice were exposed to the smoke of nine cigarettes per day, three times per day, for ten days. In the eleventh day an excisional wound was made. The control group was sham-exposed. The cigarette smoke exposure protocol was performed until euthanasia, seven days after wounding. Wound contraction was evaluated. Sections were stained with hematoxylin-eosin, Sirius red, and toluidine blue, and also immunostained for alpha-smooth muscle actin. Gene expression of Ccn2/Ctgf and Tgfb1 was evaluated by semiquantitative reverse transcriptase polymerase chain reaction (RT-PCR). Smoke-exposed animals presented delay in wound contraction; fibroblastic, inflammatory, and mast cell recruitment; re-epithelialization; myofibroblastic differentiation; and Ccn2/Ctgf and Tgfb1 gene expression. Those alterations were strain dependent. This work confirmed the deleterious effects of cigarette smoke exposure on mouse cutaneous healing depending on mouse strain and links these effects to an overexpression of Ccn2/Ctgf.
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PMID:Ccn2/Ctgf overexpression induced by cigarette smoke during cutaneous wound healing is strain dependent. 1933 61

Sympathetic nerve failure has been proposed as a contributing factor in impaired cutaneous wound healing in diabetes mellitus. Nevertheless, no studies have shown whether beta-adrenoceptor blockade through beta-blocker (e.g., propranolol) administration may alter healing of diabetic cutaneous lesions. This study evaluated macro- and microscopically the effects of propranolol administration on cutaneous wound healing in streptozotocin-induced diabetic rats. Acute diabetes was induced by a single intraperitoneal injection of streptozotocin 14 days before wounding. Animals were treated with propranolol (50 mg/kg) dissolved in drinking water; controls received water only. Administration of beta-receptor antagonist began 1 day before wounding and was continued daily until euthanasia. A full-thickness excisional lesion (1 cm(2)) was created. The wound area was measured weekly and the animals were killed 14 days after wounding. Lesions and adjacent skin were formalin-fixed and paraffin-embedded. Sections were stained with hematoxylin-eosin, Sirius red, and toluidine blue, and immunostained for CD-68, alpha-smooth muscle actin and proliferating cell nuclear antigen. The wound area was significantly smaller in the propranolol-treated group than in the control group 7 and 14 days after wounding. Inflammatory cell numbers and metalloproteinase-9 levels were reduced in the propranolol-treated group compared to the control group 14 days after wounding. Cell proliferation, mast cell number, collagen deposition, blood vessel density, and nitric oxide levels were increased in the propranolol-treated group compared to the control group 14 days after wounding. Propranolol administration improves cutaneous wound healing of hyperglycemic diabetic rats by reducing the local inflammatory response and improving subsequent phases of the repair process.
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PMID:Propranolol improves cutaneous wound healing in streptozotocin-induced diabetic rats. 1934 3

The tumour microenvironment comprises a diverse range of cells, including fibroblasts, immune cells and endothelial cells, along with extracellular matrix. In particular, fibroblasts are of significant interest as these cells are reprogrammed during tumorigenesis to become cancer-associated fibroblasts (CAFs), which in turn support cancer cell growth. MicroRNAs (miRNAs) have been shown to be involved in this intercellular crosstalk in humans. To assess whether miRNAs are also involved in the activation of fibroblasts in dogs, we cocultured primary canine skin fibroblasts with the canine mast cell tumour cell line C2 directly or with C2-derived exosomes, and measured differential abundance of selected miRNAs. Expression of the CAF markers alpha-smooth muscle actin (ACTA2) and stanniocalcin 1 confirmed the activation of our fibroblasts after coculture. We show that fibroblasts displayed significant downregulation of miR-27a and let-7 family members. These changes correlated with significant upregulation of predicted target mRNAs. Furthermore, RNA interference knockdown of miR-27a revealed that cyclin G1 (CCNG1) exhibited negative correlation at the mRNA and protein level, suggesting that CCNG1 is a target of miR-27a in canine fibroblasts and involved in their activation. Importantly, miR-27a knockdown itself resulted in fibroblast activation, as demonstrated by the formation of ACTA2 filaments. In addition, interleukin-6 (IL-6) was strongly induced in our fibroblasts when cocultured, indicating potential reciprocal signalling. Taken together, our findings are consistent with canine fibroblasts being reprogrammed into CAFs to further support cancer development and that downregulation of miR-27a may play an important role in the tumour-microenvironment crosstalk.
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PMID:Deregulation of miR-27a may contribute to canine fibroblast activation after coculture with a mast cell tumour cell line. 3213 90


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