Schwann cells secrete IGFBP5 to facilitate the growth of keloids

Abstract

Keloids (KD) are noncancerous fibroproliferative tumors exhibiting cancer-like traits, encompass aggressive unregulated growth, absence of natural regression, and a significantly high rate of recurrence. The precise molecular mechanisms underlying KD pathology remain poorly understood. In this study, we employed single-cell sequencing to examine the characteristics of cells in KD and normal scar (NS) tissue. We evaluated Schwann cells and their secretory protein IGFBP5 function in KD. Then, the recombinant IGFBP5 protein was employed to elucidate the regulatory roles of IGFBP5 in the proliferation, migration, invasion, angiogenesis, and cell cycle of keloids fibroblasts (KF). The rabbit ear scar model was utilized to ascertain the function of IGFBP5 in vivo. We demonstrated that in KD, the proportion of Schwann cells was 4.13 times that of NS. Besides, the IGFBP5 gene exhibited an expression level that was 8.02 times higher in KD Schwann cells compared to those in NS Schwann cells. High IGFBP5 expression was positively associated with the cell proliferation, migration, invasion, angiogenesis, and cell cycle of KF. Additionally, the p53/p21/Cyclin D1 pathway regulated cell cycle and promoted cell proliferation, which was suppressed after rIGFBP5 administration. These findings suggest that Schwann cells infiltrate in KD and secrete IGFBP5 protein to promote KD growth, and targeting IGFBP5 or Schwann cell infiltration could offer novel therapeutic strategies for KD.