Non-activated tissue-regeneration polypeptides (TRPs) and the preparation methods thereof are disclosed. The TRPs contain: a
protein transduction domain (PTD) making the polypeptides to permeate a
cell membrane without
cell membrane receptors; a
furin activation domain (FAD) which has at least one
proprotein convertase cleavage site and which can be cleaved by the
proprotein convertase and activate a tissue regeneration domain (TRD) in cells; and a tissue regeneration domain (TRD) which can be activated by the
proprotein convertase cleavage of the FAD to stimulate the growth or formation of tissues or to induce the regeneration of tissues. The TRPs can be practically
mass-produced by the culture of
bacteria, such as recombinant E. coli, and are in a non-activated state before
in vivo administration. Thus, their production cost is only a few tenths of the prior active proteins having uses similar thereto, and processes for their separation, purification, handling, storage and administration are significantly simple and convenient. The
in vivo administration of the TRPs can stimulate the formation or regeneration of tissues, such as bones or cartilages, or improve the
fibrosis and
cirrhosis of organs, such as kidneys, liver, lungs and heart by pharmacological mechanisims completely different from those of prior rhBMPs or TGF-β proteins. Accordingly, the TRPs will be useful as drugs having new mechanisms.