Treatments Aimed at MicroRNA Show Early Signs of Success in Scleroderma Mouse Model
Therapeutics targeting microRNA showed signs of success in mouse models of scleroderma — particularly in skin lesions with topical applications of miR-155 antagonist, according to the results of a study titled “Targeting miR-155 to Treat Experimental Scleroderma,” published in the journal Scientific Reports.
MiRNA expression, a class of naturally occurring, small non-coding RNA molecules, was found to be deregulated in fibroblasts from systemic sclerosis patients. This altered expression was particularly found for miR-155, which is up-regulated in scleroderma patients’ skin fibroblasts. Therapeutics targeting microRNAs have shown positive results in experimental skin fibrosis. However, local treatment is a more favorable strategy for localized morbidities, as several agonist or antagonist of miRNAs have been locally administered and led to successful results in mouse models of heart, brain, and muscle diseases.
A team of researchers found that miR-155 expression is increased in skin lesions from patients with either systemic or localized scleroderma. Moreover, they found that such increase correlated with the area of fibrosis.
To understand the significance of miR-155 expression increase to systemic sclerosis pathogenesis, the team investigated disease progression in mice that do not express miR-155 (MiR-155−/− mice). Researchers observed that these mice were resistant to bleomycin-induced skin fibrosis, a result that strengthens the therapeutic effect of targeting miR-155.
The team performed additional studies, showing that silencing miR-155 inhibited collagen synthesis and impaired two pro-fibrotic signaling pathways, Wnt/β-catenin and Akt. In accordance with these findings, miR-155 knockout mice were treated topically with an antagomir-155, leading to an inhibition of Wnt/β-catenin and Akt signaling pathways in mice skin upon bleomycin-induced skin fibrosis challenge.
The results suggested that miR-155 is a potential therapeutic target for dermal fibrosis treatments. Anti-miR-155 treatments are also efficacious when administrated topically, thereby preventing the occurrence of potential side effects linked to systemic therapeutics. Additional studies performed with human skin tissue are warranted to validate these initial findings and establish the potential of miR-155 targeting as a novel treatment approach for scleroderma.
Scleroderma, also known as systemic sclerosis, is a chronic systemic autoimmune disease characterized by excessive deposition of collagen, which leads to fibrosis and can ultimately lead to internal organ failure. Effective treatments targeting fibrosis in systemic sclerosis patients are lacking, so there is a need to find better therapies.