Tuesday, 28 February 2012

IGF-2 and its relationship to Dupuytren's Contracture

Today was a hard day, I was not on my feet a great amount but apparently just the thought of going back to play badminton (which I am awesome at by the way) is enough to trigger my foot into going nooooooo. From about 2:30pm today until the end of work I was in pain when sitting that just increased when I was walking and went into overdrive when I was standing. I am not sure what to make of it, on the one hand I really want and need to lose weight but I am not in a position to cycle and I am very self concious about swimming and always get ear infections (though would start using ear plugs if I started again). Does anybody in a similar position have any suggestions? I used to like running but clearly that is so far out of the question it is not even funny. I would also like to know if anyone out there has any questions about the disease or anything that I do? 

Right so with that over onto the science for today (well the light evening reading for me) I will try and keep it as simple as possible and where I can I will try and include some more background information but the main basis for this post is to talk about IGF-2 and its relationship to Dupuytren's contracture. Remember I am not an expert and I am not a doctor but I am a research scientist so I would like to think that I have a better chance of understanding these things and maybe explaining them to others than if people just tried to read them for themselves. 

For those who don't know about Dupuytren's contracture a quick google search will show you that it is a disease that is thought to share many things with Ledderhose but it occurs in the hand rather than the foot, in fact it is thought that they are basically the same condition in different parts of the body and many people who get one disease will get the other (though Dupuytren's in the hand is much more common). 

A lot of the information that I am getting for this is coming from Dupuytrens Disease Related Hyperproliferative Disorders chapter 20. 

So IGF2 is an insulin like growth factor, all this means is that is a protein that is a bit like insulin and it circulates in your blood stream. The IGFs are known to play a role in many different life processes including ageing and growth and are far to complicated to get into here and now (but feel free to ask me questions as I actually know a bit about that). Anyway it has been shown that IGF2 in particular has a role in collagen production. Collagen has been shown to be one of the main components of the lumps that form in both Dupuytren's disease (DD) and in Ledderhose disease (LD) so of course that there maybe a link between IGF2 and DD and LD is worth looking into. 

Things are not as simple as more IGF2 means more collagen. IGF2 is regulated in the bloodstream by IGF binding proteins or IGFBPs which typically stop the IGFs from binding to their receptors. IGFBP6 in particular is thought to be involved in IGF2 regulation as it binds to IGF2 10 to 100 times more than it binds to IGF1. Anyway what people have shown is that IGFBP6 which remember stops the IGF from performing its function is actually at lower levels in DD tissue. So think about that, IGBP6 which lowers levels of IGF2 is decreased, that means that there are higher active levels of IGF2 and now remember IGF2 causes collagen production and what are the lumps in DD and LD made of, Collagen. 

What some researchers have actually done is grow cells and look at them contracting, they have then looked at cells from DD patients and as a control they have used cells derived from non-diseased portions of the hand. What they find is that if you add IGF2 then you increase the contraction and if you add IGFBP6 then you decrease the contraction. They have also looked at something that is upstream of IGFBP6, so by this I mean that they look at something called TGF-B1 and this is known to decrease the levels of IGFBP6 and so increase IGF2 and so increase levels of collagen and in this case find that there are increased levels of TGF-B1 in DD cells. 

So what is the relevance of all of this? Well what do you think might happen to a DD or LD patient when you add IGFBP6 to the lump? Well of course you should decrease the levels of IGF2 and therefore decrease collagen production and therefore ease symptoms of the disease. Sounds good to me and I hope that the picture below helps to explain this to people that have not followed the above which is quite complicated.