Semaphorin 6B Research Articles

Semaphorin profiling of periodontal fibroblasts and osteoblasts.

Cells of the periodontal attachment (cementoblasts, osteoblasts, and periodontal ligament fibroblasts) are descended from a common progenitor (the cranial neural crest). During their differentiation into different cell types, these cells separate from one another to form a laminated structure. Semaphorins (and their neuropilins and plexin receptors) act as cell guidance molecules for other neural crest derivatives. It is predicted that the differential expression of these molecules will correlate with the ability of these cells to segregate. It is demonstrated that human pre-osteoblasts segregate from PDL and gingival fibroblasts in culture. In addition, these cells express different semaphorins and plexins. Semaphorins 3D and 7A were expressed preferentially in dermal fibroblasts, while semaphorin 6B was selectively expressed by pre-osteoblasts. Semaphorins 3B, 4C, 5B, and 6C and plexins B1 and C1 were expressed in reduced levels in pre-osteoblasts. Analysis of the data suggests that differential expression of semaphorins and plexins may be involved in regulating cell-sorting in the formation and regeneration of the periodontal attachment structure. Periodontal Ligament (PDL), Reverse Transcriptase Polymerase Chain-reaction (RT-PCR).

The human semaphorin 6B gene is down regulated by PPARs

The peroxisome proliferator-activated receptors (PPARs) are ligand-inducible transcription factors and belong to the nuclear hormone receptor superfamily. They form heterodimers with the retinoid X receptor and bind to specific peroxisome proliferator-response elements. The latter are direct repeat elements of two hexanucleotides with the consensus sequence TG(A/T)CCT separated by a single nucleotide spacer. Such a sequence, or a similar one, has been found in numerous PPAR-inducible genes. We developed an affinity method to isolate human genomic fragments containing binding sites for PPARs and to identify novel PPAR target genes. For this, an antibody raised against all PPAR subtypes was used. Immunoselected fragments were amplified and sequenced and one of them, ISF5148, was found to bind specifically to PPARs in gel mobility shift, supershift, and competition assays and to exhibit a down transregulation potentiality in transfection experiments under clofibrate (a PPARα agonist) treatment. ISF5148 was mapped by BLAST analysis 8.5 kb upstream of the human semaphorin 6B [(HSA)SEMA6B] gene. The latter encodes a member of the semaphorin family of axon guidance molecules. Expression of this gene in human glioblastoma T98G cells was strongly down regulated after treatment with clofibrate or Wy-14,643, two PPARα agonists. Our study establishes for the first time that PPAR activators diminish the expression of the human (HSA)SEMA6B gene. These data are relevant to the fact that PPARs are implicated in brain development, neuronal differentiation, and lipid metabolism in the central nervous system. In addition, cross talk between the peroxisome proliferator and retinoic acid pathways is suggested.

Gene expression profiling reveals multiple novel intrinsic and extrinsic factors associated with axonal regeneration failure.

In contrast to the regeneration-competent peripheral nervous system (PNS), lesions of nerve tracts within the central nervous system (CNS) lead to chronically impaired neuronal connections. We have analysed changes in gene expression patterns occurring as a consequence of postcommissural fornix transection at a time when spontaneous axonal growth has ceased at the lesion site. This was done in order to describe both extrinsic and intrinsic determinants of regeneration failure. Using a genomic approach we have identified a number of so far undetected factors such as bamacan and semaphorin 6B, which relate to chronic axonal growth arrest and therefore are promising candidates for lesion-induced axonal growth inhibitors. In addition, we observed that within the subiculum, where the fornix axons originate, neuronal Oct-6 was induced and NG2 was down-regulated, indicating that axotomized neurons as well as glial cells react at the level of gene expression to remote axotomy.

Human Semaphorin 6B [(HSA)SEMA6B], A Novel Human Class 6 Semaphorin Gene: Alternative Splicing and All-Trans-Retinoic Acid-Dependent Downregulation in Glioblastoma Cell Lines

We have identified a novel human gene related to the class 6 semaphorin family of axon guidance molecules, termed human semaphorin 6B or (HSA)SEMA6B. Two splicing variants of this gene were identified by RT-PCR: (HSA)SEMA6B.1 (short isoform) and (HSA)SEMA6B.2 (longer isoform). Computational analysis suggests that these isoforms correspond to putative secreted and transmembranous semaphorins, respectively. The levels of (HSA)SEMA6B expression were evaluated by Northern blot analysis in different tissues and in some pathological and pharmacological conditions. We observed that (HSA)SEMA6B is highly expressed in human brain and at lower levels in a variety of other tissues. Interestingly, the (HSA)SEMA6B transcript was downregulated in two different human glioblastoma cell lines (T98G and A172) upon prolonged treatment with all-trans-retinoic acid, an anti-tumor and differentiation-inducing agent.