Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
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Target Concepts:
Gene/Protein
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Query: UMLS:C0026986 (
myelodysplastic syndrome
)
14,926
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
The role of mesenchymal stromal cells (MSCs) in the pathogenesis of
myelodysplastic syndromes
(
MDS
) has been increasingly addressed, but has yet to be clearly elucidated. In this investigation, we found that
MDS
cells proliferated to a greater extent on
MDS
-derived MSCs compared to normal MSCs.
Matrix metalloproteinase 1
(MMP1), which was downregulated in
MDS
-MSCs, was identified as an inhibitory factor of
MDS
cell proliferation, given that treatment with an MMP1 inhibitor or knock-down of MMP1 in normal MSCs resulted in increased
MDS
cell proliferation. Further investigations indicated that MMP1 induced apoptosis of
MDS
cells by interacting with PAR1 and further activating the p38 MAPK pathway. Inhibition of either PAR1 or p38 MAPK can reverse the apoptosis-inducing effect of MMP1. Taken together, these data indicate that downregulation of MMP1 in MSCs of
MDS
patients may contribute to the reduced capacity of MSCs to restrict
MDS
cell proliferation, which may account for the malignant proliferation of
MDS
cells.
...
PMID:Downregulation of MMP1 in MDS-derived mesenchymal stromal cells reduces the capacity to restrict MDS cell proliferation. 2826 42
