The following is a summary of “A Positive Loop Formed by SOX11 and Periostin Upregulates TGF-β Signals Leading to Skin Fibrosis,” published in the June 2023 issue of Investigative Dermatology by Nanri et al.

Systemic sclerosis (SSc) is a chronic, heterogeneous connective tissue disease characterized by organ fibrosis, vascular injury, and autoimmunity. TGF- is essential for the development of fibrosis, including SSc. Periostin is a matricellular protein that plays a crucial function in fibrosis formation by amplifying TGF- signals. SOX11 is a transcription factor that plays multiple essential functions in embryonic organ development. 

Researchers have previously demonstrated that SOX11 induces the expression of periostin. However, the roles of the interactions between TGF- signals, periostin, and SOX11 in the pathogenesis of SSc remain unknown. In this study, they discovered that most clones of dermal fibroblasts derived from patients with SSc exhibited constitutive, high SOX11 expression, which TGF-1 substantially induces. SOX11 establishes a positive loop with periostin in SSc dermal fibroblasts to activate TGF- signals. 

Genetic deletion of Sox11 in Postn-expressing fibroblasts inhibits bleomycin-induced dermal fibrosis. In addition, they identified several fibrotic factors dependent on the TGF-/SOX11/periostin pathway in SSc dermal fibroblasts using DNA microarrays. Our findings indicate that a positive loop formed by SOX11 and periostin in fibroblasts upregulates TGF- signals, resulting in cutaneous fibrosis.

Source: sciencedirect.com/science/article/abs/pii/S0022202X22029025