The role of TrkA in the promoting wounding–healing effect of CD271 on epidermal stem cells

Abstract

CD271, a receptor of nerve growth factor (NGF), affects the biological properties of epidermal stem cells (eSCs) which are essential for skin wound closure. Tropomyosin-receptor kinase A (TrkA), another receptor of NGF, combined with CD271 has been involved with nervous system and skin keratinocytes. However, the exact role of TrkA combined with CD271 in eSCs during skin wound closure is still unclear. This study aimed to reveal the role of TrkA in the promoting wounding-healing effect of CD271 on eSCs. We obtained CD271-vo (over-expression of CD271) eSCs by lentiviral infection. K252a was used to inhibit TrkA expression. Full-thickness skin mouse wound closure model (5 mm in diameter) was used to detect the ability of CD271 over-expressed/TrkA-deficient during wound healing. The biological characteristics of eSCs and their proliferation and apoptosis were detected using immunohistochemistry and western blot. The expressions of protein kinase B (pAkt)/Akt, phosphorylated extracellular-signal-related kinase (pERK)/ERK1/2, and c-Jun N-terminal kinase (pJNK)/JNK were also detected by western blot. We found that over-expression of CD271 promoted the biological functions of eSCs. Interestingly, over-expression of CD271 in the absence of TrkA neither promoted eSCs' migration and proliferation nor promoted wound healing in a mouse model. In addition, we observed the reduced expression of pAkt/Akt and pERK/ERK1/2 following TrkA inhibition in vitro. Our studies demonstrated that the role of TrkA in the promoting wounding-healing effect of CD271 on eSCs.

The pleiotropic molecule NGF regulates the in vitro properties of fibroblasts, keratinocytes, and endothelial cells: implications for wound healing

“…HEKa cells express TrkA high-affinity and p75 low-affinity receptors, as already described in isolated primary keratinocytes, where they increase during the exponential growth phase (9), as well as in the basal layer of the epidermis, where proliferating cells reside (40), an effect mediated by TrkA. In fact, inhibition of TrkA phosphorylation reduces the proliferation of keratinocytes in culture (40), and TrkA inhibition reduces the expression of pAkt/Akt and pERK/ERK1/2, thus reducing cellular proliferation (58). Moreover, TrkA and p75 are widely expressed in cells in the soft tissues of the human oral cavity, including keratinocytes, endothelial cells, fibroblasts, and leukocytes, and in ductal and acinar cells of all types of salivary glands (46).…”

NOX2-Dependent Reactive Oxygen Species Regulate Formyl-Peptide Receptor 1-Mediated TrkA Transactivation in SH-SY5Y Cells

“…PI3K/Akt and Ras/MAPK pathways play a key role in NGF-promoted wound healing [103, 104]. These two signalling cascades are triggered by NGF-dependent phosphorylation of Y490 and Y751 residues of TrkA, which are also transphosphorylated upon FPR1 activation by N-fMLP (Figure 2(a)).…”

Research status and hot topics of the effects of skin innervation on wound healing from 1959 to 2022: A bibliometric analysis

“…Therefore, the influence of both authors in the field is high. Notably, the only Chinese author on the top 20 list, Yibing Wang from Shandong University , also published six articles in this field, but his total number of citations and average number of citations per document were the lowest, probably because research on the effect of CD271 on epidermal stem cells on wound healing is relatively niche ( 63 – 68 ), and considerable research results have been published in recent years. Furthermore, there are relatively few collaborations between China and Shandong University with other countries and institutions in this field.…”