There could be two or three different pathways of HGF signalling: one to promote angiogenesis/survival and the other to have an antifibrotic effect (Ras-Raf-MEK-1-MAPK). In a scenario where antifibrosis is a requirement and there is a presence of both Matrix metalloproteases (known for ECM degradation) and HGF, which of these would a better bet for antifibrotic activity?
HGF and MMPs - at least some of them - are increased in liver fibrosis. Further TIMPS are also induced. Expression of neither MMPs nor HGF can predict antifibrotic effects.
Thank you for your valuable feedback Dr.Beuchler.Is this a defence mechanism/response reaction of the liver to increase the MMP and HGF/other growth factors against fibrosis?How can mesenchymal stem cells(secreting MMPs,TIMPs or HGF) be therapeutic in liver fibrosis?What could be the underlying mechanism through which they can possibly suppress the hepatic stellate cell proliferation?
I suppose that upregulation of these proteins which are partly produced in hepatocytes is a defense mechanism. .I am not familiar with mesenchymal stem cells and can not answer second part of your question,
Could anybody give me a helpful answer or ideas about the question i asked above?
Dear Mr. Thej,
I don't know whether I can really answer your question (at least I would consider MMP and HGF as different story), but I would like to make some comments, concerning liver fibrosis.
As extracellular matrix proteins (ECM) like collagen are produced by activated hepatic stellate cells (HSCs), it could be a therapeutic approach if one can eliminate activated HSCs. To that end, there are several publications eg. NK cells for senescence of activated HSCs. From Stem cells, if one can differentiate into a kind of cell-type, which blocks activity of HSCs/ eliminates activated HSCs, it would be interesting?
Some types of MMPs are produced by macrophages, which digest collagen. Therefore macrophages are to some extents important against collagen accumulation. BUT: Macrophages can activate HSCs. There is a paradigm. If one can differentiate a specific type of macrophage, which produces MMPs (should be exclusively for ECM from activated HSCs, otherwise leads to side effect?), it could be an alternative, could be however probably very tough.
Hope this helps at least in part, and good luck for your research,
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