Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0026850 (muscular dystrophy)
 5,870 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Objective Tissue inhibitor of metalloproteinase-1 (TIMP-1) is a multifunctional protein that has thc capacity to modify cellular activities and to modulate matrix turnover. This paper revealed the contributive role of TIMP-1 in progressive muscular dystrophy (PMD). Methods We examined the expression and cellular localization of TIMP-1 protein using biopsied frozen muscle from patients with Duchenne muscular dystrophy (DMD), Becker muscular dystrophy (BMD), congenital muscular dystrophy (CMD) by immunohistochemistry, double immunofluorescence and Western blot analysis. Results The results of immunohistochemistry and double immunofluorescence showed that TIMP-1 was positive only in vascular endothelial cells of normal muscles. Immunohistochemistry and Western blot analysis showed that the staining intensity was distinctly increased in some dystrophic muscles of PMD for TIMP-1. Double immunofluorescence revealed that TIMP-1 strongly expressed in the regenerating muscle fibers, macrophages and macrophage infiltrating necrotic fibers. Some activated fibroblasts in endomysium and perimysium of DMD and CMD muscles were also positive for TIMP1. Conclusion The functional consequence of overexpression of TIMP-1 in the dystrophic muscles is unknown, but the elevated local expression of TIMP-1 in diseased muscles of PMD and their distinct distribution pattern provide evidence that TIMP-1 may participate in the pathogenesis of PMD.
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PMID:Expression of tissue inhibitor of metalloproteinase-1 in progression muscular dystrophy. 1768 3

Dysferlinopathy, caused by a dysferlin gene mutation, is a clinically heterogeneous autosomal recessive muscle disease characterized by progressive muscle degeneration. The dysferlin protein's functions and dysferlinopathy disease pathogenesis are not fully explored, and there is no specific treatment available that can alter the disease progression. This study uses publicly available dysferlinopathy patient microarray data to construct a gene co-expression network and investigates significant cellular pathways and their key players in dysferlinopathy pathogenesis. Extracellular matrix deposition, inflammation, mitochondrial abnormalities and protein degradation were found to be important in dysferlinopathy. Out of the hub genes, OXR1 and TIMP1 were selected through literature search as candidate genes for possible biomarker and molecular therapeutic target studies. A recently identified muscular dystrophy gene TOR1AIP1 was detected as a hub gene in dysferlinopathy. Co-expression and protein sequence feature analysis were adopted to predict TOR1AIP1's function. Our results suggest that LAP1 protein encoded by TOR1AIP1 may play a role in protein degradation possibly through transcriptional regulation in muscle tissue. These findings extend dysferlinopathy pathogenesis by presenting key genes and also suggest a novel function for a poorly characterized gene.
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PMID:Gene co-expression network analysis of dysferlinopathy: Altered cellular processes and functional prediction of TOR1AIP1, a novel muscular dystrophy gene. 2811 Aug 63