Keloids – a type of aberrant skin scarring, are characterized by excessive accumulation of collagen and extracellular matrix (ECM) arising from uncontrolled wound healing responses. Non-pathogenic, keloids are occasionally regarded as a form of benign tumor; CR6-interacting factor 1 (CRIF1) is a well-known CR6/GADD45-interacting protein, that has both nuclear and mitochondrial functions, and also exerts regulatory effects on cell growth and apoptosis.

A new study published in Scientific Reports aimed to compare cell proliferation, cell migration, collagen production and TGF-β signaling between normal fibroblasts (NFs) and keloid fibroblasts (KFs).

Here, the effects of CRIF1 deficiency were investigated in both NFs and KFs.

The results showed that cell proliferation, cell migration, collagen production and protein expressions of TGF-β, phosphorylation of Smad2 and Smad3 were all found to be higher in KFs compared to NFs. CRIF1 deficiency in NFs and KFs inhibited cell proliferation, migration and collagen production. In addition, phosphorylation of Smad2 and Smad3, which are transcription factors of collagen, was decreased. Whereas, mRNA expression levels of Smad7 and SMURF2, two important inhibitory proteins of Smad2/3, were increased, suggesting that CRIF1 may regulate collagen production.

It was inferred that CRIF1 deficiency decreases the proliferation and migration of KFs, thereby inhibiting their overgrowth via the transforming growth factor-β (TGF-β)/Smad pathway. CRIF1 may thus, represent a potential therapeutic target in keloid pathogenesis.

Source: Scientific Reports. 2021 Jan 12;11(1):500. doi: 10.1038/s41598-020-79785-y.