RhoA, RhoB, RhoC, Rac1, Cdc42, and Tc10 mRNA levels in spinal cord, sensory ganglia, and corticospinal tract neurons and long‐lasting specific changes following spinal cord injury

Abstract

Inhibition of RhoA has been shown to enhance axonal regeneration following spinal cord injury. Here we mapped mRNA expression patterns of RhoA, B, and C, Rac1, Cdc42, and Tc10 in spinal cord, sensory ganglia, and sensorimotor cortex in uninjured rats, and following spinal cord injury or sham laminectomy. In the intact spinal cord, neurons displayed high levels of Rac1, Cdc42, and Tc10 mRNA hybridization signal. GFAP-immunoreactive astrocytes expressed primarily RhoB and Rac1, while oligodendrocyte-like cells expressed RhoA, Rac1, and Cdc42. Injury caused profound, long-lasting upregulation of RhoA, Rac1, Cdc42, and Tc10 mRNA in the spinal cord, while RhoB was modestly increased and RhoC did not change. GFAP-immunoreactive reactive astrocytes exhibited a dramatic increase of RhoA mRNA expression along with increases of Rac1 and Cdc42. Injury also led to elevation of RhoA, Cdc42, and Tc10 in neurons and modest increases of RhoA, Rac1, and Tc10 in oligodendrocyte-like cells. Laminectomy caused similar, but less pronounced alterations of investigated mRNA species. In dorsal root ganglia neuronal RhoA, Rac1, Cdc42, and Tc10 mRNA levels were increased similarly by spinal cord injury and sham surgery. The CST pyramidal cells expressed Tc10 mRNA and the CST itself was Tc10-immunoreactive. Tc10-immunoreactivity disappeared distal to injury. We conclude that there are gene-specific patterns of expression of the six different Rho-GTPases in normal spinal cord and dorsal root ganglia, and that specific changes of temporal and spatial expression patterns occur in response to spinal cord injury, suggesting different roles of these GTPases in the cellular sequelae of CNS injury.

Lipocalin-2 Is an Autocrine Mediator of Reactive Astrocytosis

“…In most studies, Rho activation has been associated with an increased migratory activity of astrocytes (John et al, 2004) and other cell types (Raftopoulou and Hall, 2004;Hall, 2005), which is consistent with our results. Moreover, Erschbamer et al (2005) reported that GFAPimmunoreactive reactive astrocytes showed a marked increase of RhoA expression after spinal cord injuries, supporting the promigratory activity of Rho in reactive astrocytes. In contrast, the inhibition of Rho activities promoted astrocyte migration in a few reports (Höltje et al, 2005;Borán and García, 2007), in which the role of Rho in astrocytes may contrast with Rho-dependent mechanisms in other cell types.…”

RhoA and RhoC -siRNA inhibit the proliferation and invasiveness activity of human gastric carcinoma by Rho/PI3K/Akt pathway

“…These GTPases have been implicated in the progression of tumors from a broad range of cellular origins, and analyses at both the RNA and protein level have correlated their increased expression with tumor progression. Several Rho GTPases have been shown to regulate diverse signal transduction pathways and are involved in a variety of biological processes, including cell morphology, motility, proliferation, and apoptosis [11][12][13] . It has been known that gastric carcinogenesis is a multistep process with morphological progression involving multiple genetic and epigenetic events.…”

Cdc42 and Rac1 Signaling Are Both Required for and Act Synergistically in the Correct Formation of Myelin Sheaths in the CNS

“…In the context of CNS myelination, pathways known to influence oligodendrocyte development such as those initiated by the activation of integrin receptors (Liang et al, 2004) or the transmembrane protein Lingo-1 (Mi et al, 2005) can modulate the activities of cdc42, rac1, and rhoA. These GTPases are expressed by oligodendrocytes (Erschbamer et al, 2005), and, in primary oligodendrocyte cultures, their expression and activity are developmentally regulated (Liang et al, 2004). Although rhoA is expressed and active during early progenitor stages, the expression and activity of cdc42 and rac1 increase as differentiation proceeds (Liang et al, 2004).…”