Collagens are expressed in various types of cells, but principally by fibroblasts.  The newly formed collagen is formed as a soluble protein so that it can pass out through the cell membrane, but once expressed it must undergo post-translational processing in the extracellular space.   Like all soluble proteins, the nascent collagen has an amino-terminus and a carboxyl-terminus, but in order for the collagen segment to become part on an insoluble extracellular matrix, it is necessary to remove these termini.

The general process is shown on the right.  As the nascent collagen is expressed into the extracellular space, specific proteases for each type of collagen that cleave the termini, leaving two peptide fragments and a tropocollagen segment.  The tropocollagens self-assemble and become part of the triple helical structure that comprise Type I and III fibrilar collagens. 

The cleaved peptides are important structures in that they down-regulate further collagen production by interacting with the discoidan domain receptors, DDR1 and DDR2, which are the only RTK (receptor tyrosine kinase)-type receptors that interact with nonsoluble proteins.  The interaction between the cleaved termini and the DDR receptors initiates a negative feedback mechanism  that down-regulates further collagen synthesis.

Cascia has two drug candidates which are recombinant produced peptides that are identical to the cleaved N and C termini.  Administering a quantity of these peptide fragments reduces collagen expression in fibrotic disease states. 

This approach was validated in animals using a CCL₄ model of liver fibrosis.  Two groups of animals had induced liver fibrosis, while a third group acted as controls.  The results are shown below.

The panel on the left is representative of the control group which had no fibrosis.  The panel on the right shows dark staining of fibrotic areas in the experimental group that did not receive the peptide treatment, while the middle panel shows a reduced fibrotic area in the experimental animals after administration of the collagen peptides after seven days.  This treatment reduced both the amount of new scar tissue formation, and resolved existing scar by allowing remodeling by metalloproteinases.