Analysis of Dupuytren's Cells

So I thought it was about time for another science post, don't worry it is only going to be a short one and is again based on a chapter from the book, Dupuytren's Disease and Hyperproliferative Disorders. C. Eaton et al, Chapter 14.

Right so for those who don't know (I have explained it before but hey and see the picture below from the previous post) DNA is a constant in the cell and it is converted to mRNA in a regulated manner which is then converted into proteins which have an effect.

The central dogma 

So one way of analysing cells and differences in them is to look at the levels of mRNA. There is a technique called a Microarray and whilst I will not going into detail here what it basically does is give you a read out of the levels of mRNA for pretty much every gene, so what that means is that you have a read out of how much there is of the things that are responsible for what happens in the cell.

So what they have decided to do in this experiment is to get cells from patients with Dupuytren's disease from healthy and Dupuytren's tissue and they look at what differences there are between the 2 different types of cells using a microarray. This is then repeated, in this case on 20 patients and they look at what mRNAs are at different levels in ALL patients and from this they come up with a list of genes (genes are the DNA that codes for the mRNA) that might be linked to Dupuytren's disease.

They then cut this already small list down to ones that are likely to play a role in the development of Dupuytren's and in particular they are looking at the ones that are likely to play a role in contracture. They come up with several different proteins which I won't go into as they don't mean anything to me but they come up with things that are involved with the extracellular matrix (ECM) which plays an important role in connective tissue and I have mentioned it in my past post along with collagen.

They then go on to basically say that there are some mRNAs that are at a lower level in the disease tissue and this might be linked to the development of contracture but do not speculate as to how and how this might be useful. I guess knowing the cause if the first step towards a sure and this information helps in the understanding of the cause.

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. 

I got the book, hahahahaha

The book:

Dupuytren's Disease and Related Hyperproliferative Disorders: Principles, Research, and Clinical Perspectives

Today I was given a rather awesome late Birthday present in the form of the above book which I posted about a few weeks ago and was saying how great it would be to have it and now I do. Being a scientist I love to do my research and I really like to know how things work and be up to date with the current understanding. So of course when I found out that I had Ledderhose I wanted to know everything about it and of course there is not that much to find and then I saw this book and whilst it is mainly focused on Duputren's disease a lot of the background science such as the cells that are the main part of the lumps and the cause of both is unknown and in all likelihood the same.

So I have only had this book since late this morning and I can already seen a lot of potential to increase my understanding of the disease and I can see the potential for many useful blog posts on the science of the thing (which I will try and make friendly for the non-science community) and also on lots of other different things that I just didn't have the details on before. As regulars will know along with my usual ranting about my foot I like to post more useful things such as the types of treatments and I think I am going to follow this up by posting about risks and prevalence and symptoms etc as I also think that these will be useful and perhaps I should really have started with those to keep things in chronological order. Still I think that the book is going to be very useful for all of these things and I can't wait to get home and knowing me read it from start to finish making notes and learning as much as I can to share with those that want to know.

Having had a bit more of the book I can see that there is going to be so much that I can post now in top of my usual ramblings (see a bit further down for todays).

So I would like to say a huge thanks to JOA for getting this book for me, it is a great and generous birthday present and I couldn't have picked a better man for the job of best man.

So today was pretty good until I got on the train home and then it was like my foot knew that there was nowhere to sit and I was in a lot of pain for the 8 minute journey, I feel that without some king of proof that I have this thing there is no way I can ask people to move out of their seats on a crowded train but I don't know if anything like that exists, guess it gives me something to do this evening. Well first I am having dinner and a foot spa and then I am going to finish my Surgery post for later but then maybe I will have a look and see if there is anything I can get...