Liver Fibrosis and WISP1 antibody inhibited MRTF signaling.

     Fibrosis is the major risk factor associated with morbidity and mortality in patients with non-alcoholic steatohepatitis, (NASH), chronic liver disease.  NASH fat cells cause liver scarring which can lead to cirrhosis, and possibly cancer.  JCI.

     Liver fibrosis is the scarring of the liver tissue.  This is the first stage of liver deterioration.   The liver functions decrease until there is nothing left.  Liver failure ensues.

     Research has been unable to clearly establish the initiation mediators.  There are treatments available.  NIH.

     After a biopsy, doctors will usually assign a level of affect.  METAVIR is a popular scoring system.  A0: no activity; A1: mild activity; A2: moderate activity; A3: severe activity.  F0: no fibrosis; F1: portal fibrosis without septa; F2: portal fibrosis with few septa; F3: numerous septa without cirrhosis; F4: cirrhosis.

     With status assignment a pathway appears, involving WNT1-inducible signaling pathway protein 1 (WISP1) and myocardin-related transcription factor (MRTF). Nature.com.  This protein pathway functions as a central mechanism pushing liver fibrosis progression.  This occurs via the integrin-dependent transcriptional reprogramming of myofibroblast cytoskeleton and motility.

     Regulation of WISP proteins could improve treatments for cancer patients.

     Liver fibrosis patients are given antifibrotics.  Antifibrotics are prescribed medications which have been shown to reduce the likelihood that liver scarring will occur. 

     Research is ongoing.  In mice, WISP1 protein deficiency protects against fibrosis progression, but not fibrosis onset.  Treatment is available.  The cure hasn't been found, yet.  The therapeutic administration of a novel antibody blocking WISP1 halted the progression of existing liver fibrosis in NASH models. 

     Research on the eradication of fibrosis leads to the WISP1-MRTF axis.  This is the key to liver fibrosis progression. The aim is to target the pathway with antibody-based therapy.  Apply WISP1.  Stop MRTF. Slow down NASH.

     Thus, WISP1 antibody inhibition of MRTF signaling will prevent progression and treat NASH fibrosis.