[Immunology] Re: Osteopontin and Fibrosis

[Bryan Heit]

John H. wrote:
> Lately I've been doing some digging around in relation to idiopathic
> pulmonary fibrosis and chronic heart failure. To my surprise
> osteopontin is upregulated in both cases and is now being perceived as
> a primary driver of fibrosis. It is known that aldosterone increases
> osteopontin production (MR specific antagonists are very efficacious in
> chronic heart failure) but I'm looking for other possible causes of
> increased osteopontin production because it is doubtful that it is the
> causative factor in relation to idiopathic pulmonary fibrosis. Possible
> targets are:
> 
> tgf beta
> il-1
> tnfa
> Smad 3 or 7???
> 
> Can anyone here help me?
> 
> 
> John.

Your best bet is pubmed.gov - this page will let you search the medical 
literature for pretty much any information you want.  In terms of 
idiopathic lung fibrosis, several potential causative agents have been 
identified.  Included in that list is osteopontin, TGF-b, TNF, IL-8, 
IGF-1, leukotrienes, and a whole slew of other mediators.  As for the 
causative agent, that is unknown (hence the idiopathic).  By and large, 
it is considered to be a failure of the body to stop the wound healing 
process after some form of inflammatory damage to the lungs.  Why this 
occurs (and why it doesn't occur in the majority of people who 
experience lung inflammation) is a mystery.

Some proposed causative agents include persistent viral infections, 
unresolved or chronic inflammation, increased oxidative stress within 
the lung, genetics, and autoimmunity.  This broad spectrum of potential 
causative agents has led some people to propose that IPF may actually be 
a collection of diseases, rather then one disease, which just happen to 
share common symptoms.

Some reviews:
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=12475802&query_hl=1&itool=pubmed_DocSum
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=16500642&query_hl=4&itool=pubmed_docsum
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=16262559&query_hl=4&itool=pubmed_DocSum
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=16214821&query_hl=4&itool=pubmed_DocSum
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=16093819&query_hl=4&itool=pubmed_DocSum
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=15894605&query_hl=4&itool=pubmed_DocSum
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=15863652&query_hl=4&itool=pubmed_DocSum
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=15648777&query_hl=4&itool=pubmed_DocSum

Bryan