Disease relevance of Tmsb4x

• Up-regulation of Tb4 gene expression may be responsible for the disintegration of the musculature during the development of adenomyosis [1].
• Thymosin-beta4 regulates motility and metastasis of malignant mouse fibrosarcoma cells [2].
• We identified a thymosin-beta4 gene overexpression in malignant mouse fibrosarcoma cells (QRsP-30) that were derived from clonal weakly tumorigenic and nonmetastatic QR-32 cells by using a differential display method [2].
• In diabetic mice, where healing is delayed, we found that wound contracture and collagen deposition were significantly increased in the mice treated with thymosin beta 4 in either phosphate buffered saline solution or a hydrogel formulation [3].
• B16-F10 cells infected with adenoviruses containing a thymosin beta4 expression vector or an empty vector were injected subcutaneously and intravenously into C57BL/6 mice to evaluate tumor growth and metastatic potential, respectively [4].

High impact information on Tmsb4x

• Additionally, loading of exogenous Tbeta4 into both keratocytes and fibroblasts caused very rapid disassembly of actin filaments and reduction of cellular contractility [5].
• In vitro spectrophotofluorometric assays indicated that caged Tbeta4 did not change the normal actin polymerization kinetics, whereas photoactivated Tbeta4 significantly inhibited actin polymerization [5].
• Thymosin beta4 gene expression and cell motility/invasion were seen in the tumors from WT mice but not in those from gp91(phox-/-) mice [6].
• All of the six malignant fibrosarcoma cell lines that have been independently converted from QR-32 cells expressed high levels of thymosin-beta4 mRNA and its expression in tumor cells was correlated with tumorigenicity and metastatic potential [2].
• These findings indicate that thymosin-beta4 molecule regulates fibrosarcoma cell tumorigenicity and metastasis through actin-based cytoskeletal organization [2].

Chemical compound and disease context of Tmsb4x

• Therapeutic Potential of Thymosin-beta4 and its Derivative N-acetyl-seryl-aspartyl-lysyl-proline (Ac-SDKP) in Cardiac Healing After Infarction [7].

Biological context of Tmsb4x

• To determine how T beta 4 gene expression is regulated and how the alternative transcripts are derived, we cloned the mouse T beta 4 gene [8].
• The mouse thymosin beta 4 gene: structure, promoter identification, and chromosome localization [8].
• The Tbeta4 lines spread more fully and adhered to the dish more strongly than vector controls; this altered phenotype correlated with a twofold increase in talin and alpha5-integrin and a nearly threefold increase in vinculin [9].
• We previously showed that the -278 to +410 region of mouse thymosin beta4 (mT,beta4) gene supports high levels of reporter gene expression in NIH3T3 cells [10].
• In conclusion, the results presented here demonstrate the expression of Tbeta4 gene during early embryogenesis which immediately suggests an important role for this peptide in developmental processes requiring actin-based functions such as the formation of cardiovascular system [11].

Anatomical context of Tmsb4x

• Prothymosin alpha [corrected] (ProT alpha) and thymosin beta 4 [corrected] (T beta 4) were isolated from murine thymus and characterized by microsequence analysis [12].
• Furthermore, lymphocytes have a unique T beta 4 transcript relative to the ubiquitous transcript found in many other tissues and cells [8].
• A cDNA clone was isolated from a mouse pre-B cell line, the sequence of which has a very high homology with rat and human thymosin beta 4 genes [13].
• To determine the extent of cell adaptability to these reductions in F-actin, we overexpressed Tbeta4 in NIH 3T3 cells [9].
• Co-ordinate regulation of the cytoskeleton in 3T3 cells overexpressing thymosin-beta4 [9].

Associations of Tmsb4x with chemical compounds

• The synthetic material was also shown to be identical with the natural thymosin beta 4 by tryptic peptide mapping, amino acid compositional analyses, and polyacrylamide gel isoelectric focusing [14].
• Previously, thymosin beta 4 (Tbeta(4)) was found to promote wound healing in full thickness skin wounds and heptanol debrided corneas [15].
• Thymosin beta 4 mRNA was induced even in the presence of cycloheximide [16].
• On the other hand, cycling cells that were synchronized at different stages of the cycle by means of mitotic shake-off after nocodazole arrest or a double thymidine block did not show any variation in the levels of thymosin beta 4 mRNA when they progressed synchronously through the cycle [16].
• In this study, we examined the nucleotide sequence of the 5'-flanking region (from -2202 to -881) of the mouse Tbeta-4 gene, and demonstrated that the DNA fragment from -278 to +410 of this gene was capable of directing the expression of a chloramphenicol acetyltransferase reporter gene in NIH3T3 cells [17].

Regulatory relationships of Tmsb4x

• Up-regulation of thymosin beta 4 gene expression in experimentally-induced uterine adenomyosis in mice [1].

Other interactions of Tmsb4x

• C9 was identified as thymosin beta-4, and C15 showed extensive homology to lactotransferrin [18].
• Analysis of two multilocus mouse crosses showed that the thymosine beta4 gene, Ptmb4, is present as a single-copy gene that maps to distal Chr X. The L37a, S8, and QM clones are all members of large multilocus families [19].
• Biologically, synthetic thymosin beta 4 was found to be as active as the natural compound in a terminal deoxynucleotidyltransferase induction assay and in a macrophage migration inhibition assay [14].
• Effects of thymosin beta 4 and thymosin beta 10 on actin structures in living cells [20].

Analytical, diagnostic and therapeutic context of Tmsb4x

• In situ hybridization showed that T beta 4 mRNA was strongly expressed in the central nervous system and peripheral ganglia, paralleling the gradient of neuronal differentiation [21].
• Reverse transcriptase polymerase chain reaction (RT-PCR) was used to analyze the differential expression of the thymosin-beta gene, and reverse phase high-performance chromatography (HPLC) and mass spectroscopy were used to determine the concentration of thymosin beta4 (Tbeta4) and AcSDKP in EC lysate and in the medium (mBMEC-CM) [22].
• Isolation and structural studies of porcine, ovine and murine thymosin beta 4 by high-performance liquid chromatography [23].
• The mean numbers of metastatic lung nodules in mice (n = 20) 2 weeks after intravenous injection with thymosin beta4-expressing adenovirus and with control adenovirus were 46.7 (95% CI = 35.0 to 57.7) and 10.9 (95% CI = 6.2 to 15.6), respectively (difference = 35.8 metastatic lung nodules, P<.001) [4].
• METHODS: Northern blot analysis and immunohistochemistry were used to examine thymosin beta4 expression in mouse melanoma B16 cell lines and in B16-F10 cells derived from metastatic mouse lung tumors, respectively [4].

References