The study of hepatoprotective effect in TAA-induced liver fibrosis is in progress, and I really want to figure the key pathway out. And the classic TGFb pathway and NFkB pathway (TNFa related) are well respectively investigated in activation of HSCs. Is there any evidence to clarify the interaction between these two pathway? I could only find a few papers which focus on other tissue but not liver. Am I going in the wrong direction? Is there something I misunderstood? Or it is still unknown?
Article Mechanisms of Hepatic Fibrogenesis
Here it is said (in the Results section) that ROS
activates NF-KappaB.
http://www.jneuroinflammation.com/content/7/1/88
Maybe interesting:
http://www.idibell.cat/modul/noticies/en/438/inhibition-of-enzyme-nox4-prevents-liver-fibrosis
http://www.comparative-hepatology.com/content/6/1/9
http://www.eurekalert.org/pub_releases/2010-03/bmj-ism032210.php
http://www.eurekalert.org/pub_releases/2010-03/w-gml022510.php
http://www.eurekalert.org/pub_releases/2008-05/wjog-wrd052008.php
http://www.eurekalert.org/pub_releases/2007-12/uoc--rst121707.php
Regards,
Joachim (not a medic)
Both TGF beta and TNF release from the membrane are regulated by ADAM family members such as TACE or ADAM17 and the soluble forms activate certain pathways, but if you inhibit or regulate the activity of the ADAM members, you would affect both pathways.
I think in this paper is a possible connection in HSC described:
Eur J Cell Biol. 2001 Aug;80(8):554-61.
The bcl, NFkappaB and p53/p21WAF1 systems are involved in spontaneous apoptosis and in the anti-apoptotic effect of TGF-beta or TNF-alpha on activated hepatic stellate cells.
Saile B, Matthes N, El Armouche H, Neubauer K, Ramadori G.
Dear All:
Really thank you to provide valuable information to me, I will read them all and figure out the possible mechanism, and than share to you guys. But I have to attend the international conference these day, so I will post and update after a few days.
Eur J Cell Biol. 2001 Aug;80(8):554-61.TGF-b as well as TNF-a induced activation of NFkB and
upregulated bcl-xL observed in activation of rat HSCs.
Recently, I found a pathway which could explain all the liver fibrosis processing is about TLR4-related signal cascades. And I had share review paper below, I hope you could also give me some feedback.
To summarize, the TLR4 reflects the tissue injury signals, and it induces many different types of hepatic cells to be responsive, such as HSCs activation (fibrosis), Kupffer cells activation (inflammation), hepatocyte mortality (survival/apoptosis). Moreover, the key transcription factors of TLR4 pathway are NFkB & AP-1, and the other classic proteins (TGF-b, aSMA, COX-2, iNOS, TNFa, IL-1b) are regulated by them.
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