Researchers discover the genetic pathway that could help in the eventually help in the treatment of skin problems and cancer.
The researchers from the Oregon Health & Science University have succeeded in exposing a pathway by which demonstrates as to how a genes over-expression causes skin stem cells to change over from creating hair follicles to creating sebaceous glands.
The results of the discovery by the laboratory of Xiao-Jing Wang, M.D., Ph.D., professor of otolaryngology/head and neck surgery, OHSU School of Medicine, and member of the OHSU Cancer Institute, which is to be published in the latest issue of the journal Developmental Cell, explains that the new pathway that could one day be used as a therapeutic target for not only treating hair loss and oily skin, but also for the prevention and treatment of cancer.
The Developmental Cell study is the first to definitively link Smad7 over-expression and the pathological changes that occur in aged skin.
'In humans, scientists and medical doctors documented the aging skin phenotype a long time ago, and the Smad7 over-expression in aged skin was reported a few years ago, but nobody knew whether these two events had any link,' said Wang, who also serves in the OHSU departments of Cell and Developmental Biology, and Dermatology. 'We found the mechanism that links these two together.'
For their study, the researchers created genetically engineered mice in which Smad7 is expressed in the skin, including epidermal stem cells, with the expression level comparable to aged skin. They found that Smad7 over-expression shifts the epidermal stem cell differentiation program from forming hair follicles to sebaceous glands, causing the mice to exhibit balding and oily skin.
Surprising to the researchers was that, independent of its normal role in blocking signalling from a group of genes called Smad, Smad7 shuts down signalling of another group of genes called Wnt, by binding to a Wnt signalling protein known as Beta-catenin and degrading it with an enzyme called Smurf2. Wnt signalling is critical for organ development, but if Wnt signalling is too active, it also causes cancer.
'Our study identifies a new Beta-catenin degradation pathway,' the scientists said in the study. 'This finding has a significant impact not only on skin development and diseases, but also on diseases and cancers in other organs.'
For example, enhanced Beta-catenin signalling contributes to many cancer types, including those of the colon, lung and brain. The researchers believe inducing over-expression of Smad7 or delivery of Smad7 directly to tumour cells would provide a therapeutic approach because of the boost in Beta-catenin degradation.
However, impaired Beta-catenin signalling contributes to neurodegeneration, such as that caused by Alzheimer's disease, retina degeneration, bone density defect and aging. For these diseases, blocking Smad7-mediated Beta-catenin degradation may offer a therapeutic approach.