Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0239946 (liver fibrosis)
 8,268 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Recent studies suggest that mesenchymal stem cells (MSCs) possess a greater differentiation potential than once thought and that they have the capacity to regenerate damaged tissues/organs. However, the evidence is insufficient, and the mechanism governing the recruitment and homing of MSCs to these injured sites is not well understood. We first examined the MSCs circulating in peripheral blood and then performed chemotaxis, wound healing and tubule-formation assays to investigate the migration capability of mouse bone marrow MSCs (mBM-MSCs) in response to liver-injury signals. In addition, BM-MSCs from donor enhanced green fluorescent protein transgenic male mice were transplanted into liver-injured co-isogenic female recipients, either by intra-bone marrow injection or through the caudal vein, to allow in vivo tracking analysis of the cell fate after transplantation. Donor-derived cells were analysed by in vivo imaging analysis, PCR, flow cytometry and frozen sections. Microarray and real-time PCR were used for chemokine/cytokine and receptor analyses. We successfully isolated circulating MSCs in peripheral blood of liver-injured mice and provided direct evidence that mBM-MSCs could be mobilized into the circulation and recruited into the liver after stimulation of liver injury. CCR9, CXCR4 and c-MET were essential for directing cellular migration towards the injured liver. The recruited mBM-MSCs may play different roles, including hepatic fate specification and down-regulation of the activity of hepatic stellate cells which inhibits over-accumulation of collagen and development of liver fibrosis. Our results provide new insights into liver repair involving endogenous BM-MSCs and add new information for consideration when developing clinical protocols involving the MSCs.
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PMID:Recruitment of endogenous bone marrow mesenchymal stem cells towards injured liver. 1978 Aug 71

Liver fibrosis is a gradual process of increased secretion and decreased degradation of extra-cellular materials. Two cell types are now well recognized as being involved in liver fibrosis, i.e. hepatic stellate cells (HSCs) and portal mesenchymal cells. T iis process is initiated by the damage of hepatic cells, which leads to activation of hepatic stellate cells that differentiate into myofibroblasts leading to the formation of liver fibrosis. On the other hand, the epithelial-mesenchymal transition and mesenchymal-epithelial transition are crucial for the regulation of cellular plasticity during liver fibrosis. The EMT is a process in which molecular reprogramming leads epithelial cells to adopt a mesenchymal phenotype. During EMT, epithelial cells gain mesenchymal features which include changes in the expression of epithelial markers. The EMT process plays fundamental roles during embryogenesis, tissue fibrosis, and carcinogenesis. As multiple experimental studies of liver fibrosis have confirmed that established liver fibrosis is reversible upon cessation of the causative agent, modulation of the EMT markers could be promising as potential therapeutic agents. Better understanding of the molecular cascades of intracellular fibrogenic signaling and genetic factors that controlling the expression of EMT markers would be a powerful strategy for early diagnosis and treatment liver fibrosis at the genetic level. Activating or silencing of the responsible genes may be an efficient and more specific approach for treating liver fibrosis either through the arrest of EMT or the induction of MET.
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PMID:ROLE OF EPITHELIAL MESENCHYMAL TRANSITION IN HEPATIC FIBROGENESIS. 2648 54