Title : Interleukin 11 drives dermal fibroblast activation in mechanical stretch-mediated skin expansion
Abstract:
Skin expansion is a commonly used method to generate additional skin for the repair of tissue abnormalities in many circumstances, including post-traumatic scars, congenital defects, and skin defects following tumor excision. This is accomplished by inducing skin regeneration using Mechanical Stretch (MS). However, the primary obstacles associated with this procedure are the lengthy treatment duration, attributable to the limitations of skin regeneration speed. The prolonged period may lead to problems such as skin necrosis and suboptimal skin texture.
Therefore, it is essential to improve our understanding of the pathophysiological mechanisms related to skin expansion, particularly the processes involved in dermal regeneration, given that dermal fibroblasts are the primary cellular constituents of the dermis, and MS facilitates their activation. The precise function of interleukin 11 (IL11) in skin growth is not fully understood, however it has been recognized as a cytokine responsive to mechanical stimulation.
This study indicated that the expression of IL11 and the IL11 receptor alpha subunit was significantly elevated in dermal fibroblasts of Expanded Skins (ESs), and that diminished IL11 expression was associated with inadequate regeneration of ESs. Inhibition of IL11 signaling led to reduced MS-induced fibroblast proliferation, extracellular matrix synthesis, and myofibroblast activation in vitro, along with compromised skin regeneration during skin expansion in vivo. We identified that WNT5B acted as a downstream regulator of IL11-induced cell activation in the presence of MS. The administration of recombinant IL11 through intradermal injection in mice markedly increased fibroblast activation and inhibited the decrease in dermal thickness during skin expansion.
In conclusion, our study's findings indicate that IL11 signaling is crucial for fibroblast activation induced by MS, making it a potential target for clinical applications to enhance skin regeneration during skin expansion.
