Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0002871 (anemia)
 52,094 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

KIT is a receptor tyrosine kinase that after binding to its ligand stem cell factor activates signaling cascades linked to biological processes such as proliferation, differentiation, migration and cell survival. Based on studies performed on SCF and/or KIT mutant animals that presented anemia, sterility, and/or pigmentation disorders, KIT signaling was mainly considered to be involved in the regulation of hematopoiesis, gametogenesis, and melanogenesis. More recently, novel animal models and ameliorated cellular and molecular techniques have led to the discovery of a widen repertoire of tissue compartments and functions that are being modulated by KIT. This is the case for the lung, heart, nervous system, gastrointestinal tract, pancreas, kidney, liver, and bone. For this reason, the tyrosine kinase inhibitors that were originally developed for the treatment of hemato-oncological diseases are being currently investigated for the treatment of non-oncological disorders such as asthma, rheumatoid arthritis, and alzheimer's disease, among others. The beneficial effects of some of these tyrosine kinase inhibitors have been proven to depend on KIT inhibition. This review will focus on KIT expression and regulation in healthy and pathologic conditions other than cancer. Moreover, advances in the development of anti-KIT therapies, including tyrosine kinase inhibitors, and their application will be discussed.
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PMID:KIT as a therapeutic target for non-oncological diseases. 3055 30

Exposure to spaceflight and microgravity causes physiologic and psychologic changes including bone loss, cardiovascular dysfunction, and immune dysfunction. Anemia and hematopoietic disorders are observed in astronauts after spaceflight. Hematopoietic stem and progenitor cells (HSPCs), which can self-renew and give rise to all blood cells, play vital roles in hematopoiesis and homeostasis; however, the molecular mechanisms responsible for the impacts of microgravity on the proliferation of HSPCs remain unclear. We maintained mouse bone marrow HSPCs in the presence of stem cell factor for 12 d under spaceflight and simulated microgravity conditions, respectively, and analyzed cell proliferation and gene expression. Both spaceflight and simulated microgravity significantly decreased the number of HSPCs, mainly by blocking cell cycle at G1/S transition, but did not affect their differentiation abilities. RNA-sequencing data indicated that genes related to cell proliferation were down-regulated, whereas the genes related to cell death were up-regulated under microgravity. Among the gene signatures, we identified that the Kit-Ras/cAMP-cAMP response element-binding protein pathway might be one of the major microgravity-regulated pathways during HSPC proliferation. Furthermore, the quantification of notable genes was validated at the mRNA levels under simulated microgravity condition. Overall, these results would help us to understand the intracellular molecular mechanisms regulating microgravity-inhibited proliferation of HSPCs.-Wang, P., Tian, H., Zhang, J., Qian, J., Li, L., Shi, L., Zhao, Y. Spaceflight/microgravity inhibits the proliferation of hematopoietic stem cells by decreasing Kit-Ras/cAMP-CREB pathway networks as evidenced by RNA-Seq assays.
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PMID:Spaceflight/microgravity inhibits the proliferation of hematopoietic stem cells by decreasing Kit-Ras/cAMP-CREB pathway networks as evidenced by RNA-Seq assays. 3072 27


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