Rho GTPases in hematopoietic stem/progenitor cell migration.
ABSTRACT Rho GTPases including RhoA, Rac1, and Cdc42 are a class of intracellular signaling proteins critical for the regulation of cytoskeleton organization, adhesion, and migration. Molecular mechanisms of mammalian cell migration were first revealed in fibroblasts where RhoA, Rac1, and Cdc42 facilitate in the multistep process including establishment and maintenance of polarity, formation of actin-rich protrusions, remodeling of adhesive contacts, and generation of force. In hematopoietic stem/progenitor cells, Rho GTPases relay signals from chemokines and cytokines such as SDF-1α and SCF to the actin and microtubule cytoskeleton through effector kinases and/or adaptor molecules that affect adhesion or transcription. Comprehensive use of murine conditional gene knockout technology combined with biochemical approaches in recent studies allows for physiologically relevant investigations of the involvement of Rho GTPases in hematopoietic stem/progenitor cell migration, providing important mechanisms for the stem/progenitor maintenance.
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ABSTRACT: The characteristics of renal tubular progenitor/precursor cells and the role of renal tubule regeneration in the repair of remnant kidneys (RKs) after nephrectomy are not well known. In the present study of a murine model of subtotal nephrectomy, we used immunofluorescence (IF), immunoblot analysis and in situ hybridization methods to demonstrate that nestin expression was transiently upregulated in tubule cells near the incision edges of RKs. The nestin-positive tubules were immature proximal tubules that co-labeled with lotus tetragonolobus agglutinin, but not with markers of mature tubules (Aquaporin-1, Tamm-Horsfall protein, Aquaporin-2). In addition, many of the nestin-expressing tubule cells were actively proliferative cells, as indicated by co-labeling with bromodeoxyuridine. Double-label IF and immunoblot analysis also showed that the upregulation of tubular nestin was associated with enhanced transforming growth factor-β1 (TGF-β1) expression in the incision edge of RKs, but not α-smooth muscle actin, which is a marker of fibrosis. In cultured human kidney proximal tubule cells (HKC), immunoblot analysis indicated that TGF-β1 induced nestin expression and loss of E-cadherin expression, suggesting an association of nestin expression and cellular dedifferentiation. Knock down of nestin expression by a shRNA-containing plasmid led to decreased migration of HKC cells that were induced by TGF-β1. Taken together, our results suggest that the tubule repair which occurs during recovery process following nephrectomy may involve TGF-β1 induced nestin expression in immature renal proximal tubule cells and the promotion of renal cell migration.AJP Renal Physiology 09/2012; 303(11). DOI:10.1152/ajprenal.00083.2012 · 4.42 Impact Factor
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ABSTRACT: Light-emitting diode (LED) irradiation is potentially a photostimulator to manipulate cell behavior by opsin-triggered phototransduction and thermal energy supply in living cells. Directional stem cell motility is critical for the efficiency and specificity of stem cells in tissue repair. We explored that green LED (530 nm) irradiation directed the human orbital fat stem cells (OFSCs) to migrate away from the LED light source through activation of extracellular signal-regulated kinases (ERK)/MAP kinase/p38 signaling pathway. ERK inhibitor selectively abrogated light-driven OFSC migration. Phosphorylation of these kinases as well as green LED irradiation-induced cell migration was facilitated by increasing adenosine triphosphate (ATP) production in OFSCs after green LED exposure, and which was thermal stress-independent mechanism. OFSCs, which are multi-potent mesenchymal stem cells isolated from human orbital fat tissue, constitutionally express three opsins, i.e. retinal pigment epithelium-derived rhodopsin homolog (RRH), encephalopsin (OPN3) and short-wave-sensitive opsin 1 (OPN1SW). However, only two non-visual opsins, i.e. RRH and OPN3, served as photoreceptors response to green LED irradiation-induced OFSC migration. In conclusion, stem cells are sensitive to green LED irradiation-induced directional cell migration through activation of ERK signaling pathway via a wavelength-dependent phototransduction.Biomaterials 12/2012; 34(8). DOI:10.1016/j.biomaterials.2012.11.065 · 8.31 Impact Factor