Skin Fibrosis Research

Fibrosis is the formation of excess fibrous connective tissue in an organ or tissue.

Skin or cutaneous fibrosis is caused by the accumulation of extracellular matrix components in the dermis.  It occurs naturally during wound repair and scar formation but can also be the result of pathological processes in pro-fibrotic diseases.

Systemic sclerosis (SSc) or scleroderma is one of these diseases.  The word scleroderma comes from two Greek words – sclero meaning hard and derma meaning skin.  This disease is characterized by the thickening of the skin due to the excessive deposition of collagen and other extracellular matrix components.  Currently there is no cure, just treatment for various symptoms e.g. heartburn, slow bowel motion.

Luong et al have developed an artificial molecule, the histidine-pyridine-histidine ligand derivative HPH-15, which may have an antifibrotic effect.  Recently the effects of this drug were evaluated in human skin fibroblasts and in a mouse model of SSc.  Their results indicate that HPH-15 inhibits TGF-β/Smad signaling and fibrogenic activity of human skin fibroblasts in vitro and attenuates skin inflammation and subsequent fibrosis in a mouse model of SSc.   HPH-15 could potentially be used in SSc clinical trials.

Luong,V.H., Chino,T., Oyama,N., Matsushita,T., Sasaki,Y., Ogura,D., Niwa,S-i., Biswas,T., Hamasaki,A., Fujita,M., Okamoto,Y., Otsuka,M., Ihn,H. and Hasegawa,M. (2018) Blockade of TGF-β/Smad signaling by the small compound HPH-15 ameliorates experimental skin fibrosis.  Arthritis Research & Therapy 20, 46.