Home About us Contact
|
Home About us Contact | ||
|
|
||
Specific Signaling Pathways (specific + signaling_pathway)
Selected AbstractsDivided loyalties: transdetermination and the genetics of tissue regenerationBIOESSAYS, Issue 6 2006Joel C. Eissenberg Most tissues contain cells capable of the self-renewal and differentiation necessary to maintain tissue and organ integrity. These somatic stem cells are generally thought to have limited developmental potential. The mechanisms that restrict cell fate decisions in somatic stem cells are only now being understood. This understanding will be important in the clinical exploitation of adult stem cells in tissue repair and replacement. Experiments performed over fifty years ago in Drosophila showed that developmental restriction could be relaxed in the proliferating larval cells that are destined to form the adult fly integument. This phenomenon, called transdetermination, can serve as a model for mechanisms of stem-cell commitment. A recent publication1 sheds new light on the mechanism of transdetermination by demonstrating that loss of homeotic gene silencing leads to increased frequency of transdetermination. In addition, the authors link a specific signaling pathway induced by tissue regeneration to the relaxation of homeotic gene silencing. The data identify key mechanisms that control developmental homeostasis and cell fate restriction that could be manipulated to make somatic stem-cell engineering possible. BioEssays 28: 574,577, 2006. © 2006 Wiley Periodicals, Inc. [source] Recent advances in craniofacial morphogenesisDEVELOPMENTAL DYNAMICS, Issue 9 2006Yang Chai Abstract Craniofacial malformations are involved in three fourths of all congenital birth defects in humans, affecting the development of head, face, or neck. Tremendous progress in the study of craniofacial development has been made that places this field at the forefront of biomedical research. A concerted effort among evolutionary and developmental biologists, human geneticists, and tissue engineers has revealed important information on the molecular mechanisms that are crucial for the patterning and formation of craniofacial structures. Here, we highlight recent advances in our understanding of evo,devo as it relates to craniofacial morphogenesis, fate determination of cranial neural crest cells, and specific signaling pathways in regulating tissue,tissue interactions during patterning of craniofacial apparatus and the morphogenesis of tooth, mandible, and palate. Together, these findings will be beneficial for the understanding, treatment, and prevention of human congenital malformations and establish the foundation for craniofacial tissue regeneration. Developmental Dynamics 235:2353,2375, 2006. © 2006 Wiley-Liss, Inc. [source] Prostaglandin F2, inhibits adipocyte differentiation via a G,q-Calcium-Calcineurin-Dependent signaling pathwayJOURNAL OF CELLULAR BIOCHEMISTRY, Issue 1 2007Li Liu Abstract Prostaglandin F2, (PGF2,) is a potent physiological inhibitor of adipocyte differentiation, however the specific signaling pathways and molecular mechanisms involved in mediating its anti-adipogenic effects are not well understood. In the current study, we now provide evidence that PGF2, inhibits adipocyte differentiation via a signaling pathway that requires heterotrimeric G-protein G,q subunits, the elevation of the intracellular calcium concentration ([Ca2+]i), and the activation of the Ca2+/calmodulin-regulated serine/threonine phosphatase calcineurin. We show that while this pathway acts to inhibit an early step in the adipogenic cascade, it does not interfere with the initial mitotic clonal expansion phase of adipogenesis, nor does it affect either the expression, DNA binding activity or differentiation-induced phosphorylation of the early transcription factor C/EBP,. Instead, we find that PGF2, inhibits adipocyte differentiation via a calcineurin-dependent mechanism that acts to prevent the expression of the critical pro-adipogenic transcription factors PPAR, and C/EBP,. Furthermore, we demonstrate that the inhibitory effects of PGF2, on both the expression of PPAR, and C/EBP, and subsequent adipogenesis can be attenuated by treatment of preadipocytes with the histone deacetylase (HDAC) inhibitor trichostatin A. Taken together, these results indicate that PGF2, inhibits adipocyte differentiation via a G,q-Ca2+ -calcineurin-dependent signaling pathway that acts to block expression of PPAR, and C/EBP, by a mechanism that appears to involves an HDAC-sensitive step. J. Cell. Biochem. 100: 161,173, 2007. © 2006 Wiley-Liss, Inc. [source] Selective expression of connective tissue growth factor in fibroblasts in vivo promotes systemic tissue fibrosisARTHRITIS & RHEUMATISM, Issue 5 2010Sonali Sonnylal Objective Connective tissue growth factor (CTGF) is a cysteine-rich secreted matricellular protein involved in wound healing and tissue repair. Enhanced and prolonged expression of CTGF has been associated with tissue fibrosis in humans. However, questions remain as to whether CTGF expression alone is sufficient to drive fibrosis. This study was undertaken to investigate whether CTGF alone is sufficient to cause fibrosis in intact animals and whether its effects are mediated through activation of transforming growth factor , (TGF,) signaling or through distinct signal transduction pathways. Methods We generated mice overexpressing CTGF in fibroblasts under the control of the fibroblast-specific collagen ,2(I) promoter enhancer. Tissues such as skin, lung, and kidney were harvested for histologic analysis. Mouse embryonic fibroblasts were prepared from embryos (14.5 days postcoitum) for biochemical analysis. Results Mice overexpressing CTGF in fibroblasts were susceptible to accelerated tissue fibrosis affecting the skin, lung, kidney, and vasculature, most notably the small arteries. We identified a marked expansion of the myofibroblast cell population in the dermis. RNA analysis of transgenic dermal fibroblasts revealed elevated expression of key matrix genes, consistent with a fibrogenic response. CTGF induced phosphorylation of p38, ERK-1/2, JNK, and Akt, but not Smad3, in transgenic mouse fibroblasts compared with wild-type mouse fibroblasts. Transfection experiments showed significantly increased basal activity of the CTGF and serum response element promoters, and enhanced induction of the CTGF promoter in the presence of TGF,. Conclusion These results demonstrate that selective expression of CTGF in fibroblasts alone causes tissue fibrosis in vivo through specific signaling pathways, integrating cues from the extracellular matrix into signal transduction pathways to orchestrate pivotal biologic responses relevant to tissue repair and fibrosis. [source] | ||||||||||