Ribosomal S-6 Kinase Mediates Development of Liver Fibrosis

[Guest guest]

Ribosomal S-6 Kinase Mediates Development of Liver Fibrosis

By Will Boggs, MD

NEW YORK (Reuters Health) Jan 08 - The ribosomal S-6 kinase (RSK)-C/EBP-beta

phosphorylation pathway is critical for the development of liver fibrosis,

according to a report in the December 26th PLoS.

" We are working in collaboration with other groups to develop small molecules

active in this pathway, " Dr. a Buck from University of California, San

Diego, California told Reuters Health. " There is hope to cure hepatic fibrosis

through the development of this and similar technologies. "

Dr. Buck and Dr. Chojkier used a mouse model of liver injury and fibrosis

to investigate the role of RSK and phosphorylation of C/EBP-beta on Thr217 in

hepatic stellate cells (HSC) in the development of liver fibrosis.

All mice with wild-type C/EBP-beta (having Thr217) developed severe liver

fibrosis after exposure to carbon tetrachloride, the authors report, while mice

with C/EBP-beta bearing Ala217 instead of Thr217 had minimal or no fibrosis.

Blocking phosphorylation of C/EBP-beta-Thr217 by inhibiting RSK activity also

decreased the fibrotic response of the liver to chronic injury.

Mice expressing the RSK-inhibitory transgene (C/EBP-beta-Ala217) proved to be

resistant to hepatotoxin-induced liver inflammation and HSC activation and

proliferation.

Moreover, the investigators say, a C/EBP-beta-Ala217 peptide able to permeate

cells stimulated cell death in hepatotoxin-induced activation of HSC and

inhibited progression and stimulated regression of hepatotoxin-induced liver

fibrosis.

Activated HSC in biopsies of human liver fibrosis showed increased expression of

active RSK and C/EBP-beta Thr266 (the human equivalent of Thr217), the

researchers note.

" This study suggests that blocking RSK activity inhibits fibrogenesis directly

by inducing HSC apoptosis, and indirectly, by reducing liver injury and

inflammation, " the authors conclude. " We speculate that these findings may

facilitate the development of small molecules potentially useful in the

prevention and treatment of liver fibrosis. "

PLoS 2007;2:e1372

http://www.medscape.com/viewarticle/568476?src=mp

_________________________________________________________________

Shed those extra pounds with MSN and The Biggest Loser!!

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[Guest guest]

Ribosomal S-6 Kinase Mediates Development of Liver Fibrosis

By Will Boggs, MD

NEW YORK (Reuters Health) Jan 08 - The ribosomal S-6 kinase (RSK)-C/EBP-beta

phosphorylation pathway is critical for the development of liver fibrosis,

according to a report in the December 26th PLoS.

" We are working in collaboration with other groups to develop small molecules

active in this pathway, " Dr. a Buck from University of California, San

Diego, California told Reuters Health. " There is hope to cure hepatic fibrosis

through the development of this and similar technologies. "

Dr. Buck and Dr. Chojkier used a mouse model of liver injury and fibrosis

to investigate the role of RSK and phosphorylation of C/EBP-beta on Thr217 in

hepatic stellate cells (HSC) in the development of liver fibrosis.

All mice with wild-type C/EBP-beta (having Thr217) developed severe liver

fibrosis after exposure to carbon tetrachloride, the authors report, while mice

with C/EBP-beta bearing Ala217 instead of Thr217 had minimal or no fibrosis.

Blocking phosphorylation of C/EBP-beta-Thr217 by inhibiting RSK activity also

decreased the fibrotic response of the liver to chronic injury.

Mice expressing the RSK-inhibitory transgene (C/EBP-beta-Ala217) proved to be

resistant to hepatotoxin-induced liver inflammation and HSC activation and

proliferation.

Moreover, the investigators say, a C/EBP-beta-Ala217 peptide able to permeate

cells stimulated cell death in hepatotoxin-induced activation of HSC and

inhibited progression and stimulated regression of hepatotoxin-induced liver

fibrosis.

Activated HSC in biopsies of human liver fibrosis showed increased expression of

active RSK and C/EBP-beta Thr266 (the human equivalent of Thr217), the

researchers note.

" This study suggests that blocking RSK activity inhibits fibrogenesis directly

by inducing HSC apoptosis, and indirectly, by reducing liver injury and

inflammation, " the authors conclude. " We speculate that these findings may

facilitate the development of small molecules potentially useful in the

prevention and treatment of liver fibrosis. "

PLoS 2007;2:e1372

http://www.medscape.com/viewarticle/568476?src=mp

_________________________________________________________________

Shed those extra pounds with MSN and The Biggest Loser!!

http://biggestloser.msn.com/

[Guest guest]

Ribosomal S-6 Kinase Mediates Development of Liver Fibrosis

By Will Boggs, MD

NEW YORK (Reuters Health) Jan 08 - The ribosomal S-6 kinase (RSK)-C/EBP-beta

phosphorylation pathway is critical for the development of liver fibrosis,

according to a report in the December 26th PLoS.

" We are working in collaboration with other groups to develop small molecules

active in this pathway, " Dr. a Buck from University of California, San

Diego, California told Reuters Health. " There is hope to cure hepatic fibrosis

through the development of this and similar technologies. "

Dr. Buck and Dr. Chojkier used a mouse model of liver injury and fibrosis

to investigate the role of RSK and phosphorylation of C/EBP-beta on Thr217 in

hepatic stellate cells (HSC) in the development of liver fibrosis.

All mice with wild-type C/EBP-beta (having Thr217) developed severe liver

fibrosis after exposure to carbon tetrachloride, the authors report, while mice

with C/EBP-beta bearing Ala217 instead of Thr217 had minimal or no fibrosis.

Blocking phosphorylation of C/EBP-beta-Thr217 by inhibiting RSK activity also

decreased the fibrotic response of the liver to chronic injury.

Mice expressing the RSK-inhibitory transgene (C/EBP-beta-Ala217) proved to be

resistant to hepatotoxin-induced liver inflammation and HSC activation and

proliferation.

Moreover, the investigators say, a C/EBP-beta-Ala217 peptide able to permeate

cells stimulated cell death in hepatotoxin-induced activation of HSC and

inhibited progression and stimulated regression of hepatotoxin-induced liver

fibrosis.

Activated HSC in biopsies of human liver fibrosis showed increased expression of

active RSK and C/EBP-beta Thr266 (the human equivalent of Thr217), the

researchers note.

" This study suggests that blocking RSK activity inhibits fibrogenesis directly

by inducing HSC apoptosis, and indirectly, by reducing liver injury and

inflammation, " the authors conclude. " We speculate that these findings may

facilitate the development of small molecules potentially useful in the

prevention and treatment of liver fibrosis. "

PLoS 2007;2:e1372

http://www.medscape.com/viewarticle/568476?src=mp

_________________________________________________________________

Shed those extra pounds with MSN and The Biggest Loser!!

http://biggestloser.msn.com/

[Guest guest]

Ribosomal S-6 Kinase Mediates Development of Liver Fibrosis

By Will Boggs, MD

NEW YORK (Reuters Health) Jan 08 - The ribosomal S-6 kinase (RSK)-C/EBP-beta

phosphorylation pathway is critical for the development of liver fibrosis,

according to a report in the December 26th PLoS.

" We are working in collaboration with other groups to develop small molecules

active in this pathway, " Dr. a Buck from University of California, San

Diego, California told Reuters Health. " There is hope to cure hepatic fibrosis

through the development of this and similar technologies. "

Dr. Buck and Dr. Chojkier used a mouse model of liver injury and fibrosis

to investigate the role of RSK and phosphorylation of C/EBP-beta on Thr217 in

hepatic stellate cells (HSC) in the development of liver fibrosis.

All mice with wild-type C/EBP-beta (having Thr217) developed severe liver

fibrosis after exposure to carbon tetrachloride, the authors report, while mice

with C/EBP-beta bearing Ala217 instead of Thr217 had minimal or no fibrosis.

Blocking phosphorylation of C/EBP-beta-Thr217 by inhibiting RSK activity also

decreased the fibrotic response of the liver to chronic injury.

Mice expressing the RSK-inhibitory transgene (C/EBP-beta-Ala217) proved to be

resistant to hepatotoxin-induced liver inflammation and HSC activation and

proliferation.

Moreover, the investigators say, a C/EBP-beta-Ala217 peptide able to permeate

cells stimulated cell death in hepatotoxin-induced activation of HSC and

inhibited progression and stimulated regression of hepatotoxin-induced liver

fibrosis.

Activated HSC in biopsies of human liver fibrosis showed increased expression of

active RSK and C/EBP-beta Thr266 (the human equivalent of Thr217), the

researchers note.

" This study suggests that blocking RSK activity inhibits fibrogenesis directly

by inducing HSC apoptosis, and indirectly, by reducing liver injury and

inflammation, " the authors conclude. " We speculate that these findings may

facilitate the development of small molecules potentially useful in the

prevention and treatment of liver fibrosis. "

PLoS 2007;2:e1372

http://www.medscape.com/viewarticle/568476?src=mp

_________________________________________________________________

Shed those extra pounds with MSN and The Biggest Loser!!

http://biggestloser.msn.com/