The role of TrkA in the promoting wounding–healing effect of CD271 on epidermal stem cells
- 111 Downloads
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.
KeywordsEpidermal stem cells CD271 TrkA Skin wound healing Cell proliferation
Epidermal growth receptor
Epidermal stem cells
Nerve growth factor
Transit amplifying cells
Yibing Wang and Xiaohong Li conceived and designed the experiments; Min Zhang performed the experiments; Yuehou Zhang and Jiaxu Ma contributed reagents, materials, and analysis tools; Jun Ding, Siyuan Yin and Yongqian Cao analyzed the data; Xiaohong Li and Min Zhang wrote the paper; Xiaohong Li, Faming Tian, Yuan Li, and Jun Ding review the paper and references.
This study was funded by the National Natural Science Foundation of China (No. 81571911 and 81772092), and Science and Technology Development Program of Shandong Province (No. 2016GSF201080).
Compliance with ethical standards
Conflict of interest
The authors declared that no conflict of interests.
All involved animals were performed according to the National Institutes of Health (NIH) Guide. Under pentobarbital sodium anesthesia, all surgeries were performed. Followed by the Committee on the Ethics of Shandong University, the experiments were approved.
- 3.Boulton TG, Nye SH, Robbins DJ, Ip NY, Radziejewska E, Morgenbesser SD, DePinho RA, Panayotatos N, Cobb MH, Yancopoulos GD (1991) ERKs: a family of protein-serine/threonine kinases that are activated and tyrosine phosphorylated in response to insulin and NGF. Cell 65:663–675CrossRefPubMedGoogle Scholar
- 7.Chae CH, Jung SL, An SH, Park BY, Wang SW, Cho IH, Cho JY, Kim HT (2009) Treadmill exercise improves cognitive function and facilitates nerve growth factor signaling by activating mitogen-activated protein kinase/extracellular signal-regulated kinase1/2 in the streptozotocin-induced diabetic rat hippocampus. Neuroscience 164:1665–1673. https://doi.org/10.1016/j.neuroscience.2009.09.075 CrossRefPubMedGoogle Scholar
- 8.Chen J, Li Y, Hao H, Li C, Du Y, Hu Y, Li J, Liang Z, Li C, Liu J, Chen L (2015) Mesenchymal stem cell conditioned medium promotes proliferation and migration of alveolar epithelial cells under septic conditions in vitro via the JNK-P38 signaling pathway. Cell Physiol Biochem 37:1830–1846. https://doi.org/10.1159/000438545 CrossRefPubMedGoogle Scholar
- 12.Dedoni S, Olianas MC, Ingianni A, Onali P (2014) Type I interferons up-regulate the expression and signalling of p75 NTR/TrkA receptor complex in differentiated human SH-SY5Y neuroblastoma cells. Neuropharmacology 79:321–334. https://doi.org/10.1016/j.neuropharm.2013.12.002 CrossRefPubMedGoogle Scholar
- 21.Kanaji N, Nelson A, Wang X, Sato T, Nakanishi M, Gunji Y, Basma H, Michalski J, Farid M, Rennard SI, Liu X (2013) Differential roles of JNK, ERK1/2, and p38 mitogen-activated protein kinases on endothelial cell tissue repair functions in response to tumor necrosis factor-alpha. J Vasc Res 50:145–156. https://doi.org/10.1159/000345525 CrossRefPubMedGoogle Scholar
- 22.Kashiwai K, Kajiya M, Matsuda S, Ouhara K, Takeda K, Takata T, Kitagawa M, Fujita T, Shiba H, Kurihara H (2016) Distinction between cell proliferation and apoptosis signals regulated by brain-derived neurotrophic factor in human periodontal ligament cells and gingival epithelial cells. J Cell Biochem 117:1543–1555. https://doi.org/10.1002/jcb.25446 CrossRefPubMedGoogle Scholar
- 23.Khwaja FS, Quann EJ, Pattabiraman N, Wynne S, Djakiew D (2008) Carprofen induction of p75NTR-dependent apoptosis via the p38 mitogen-activated protein kinase pathway in prostate cancer cells. Mol Cancer Ther 7:3539–3545. https://doi.org/10.1158/1535-7163.mct-08-0512 CrossRefPubMedPubMedCentralGoogle Scholar
- 25.Kumar V, Gupta AK, Shukla RK, Tripathi VK, Jahan S, Pandey A, Srivastava A, Agrawal M, Yadav S, Khanna VK, Pant AB (2015) Molecular mechanism of switching of TrkA/p75(NTR) signaling in monocrotophos induced neurotoxicity. Sci Rep 5:14038. https://doi.org/10.1038/srep14038 CrossRefPubMedPubMedCentralGoogle Scholar
- 27.Latifi-Pupovci H, Kuci Z, Wehner S, Bonig H, Lieberz R, Klingebiel T, Bader P, Kuci S (2015) In vitro migration and proliferation (“wound healing”) potential of mesenchymal stromal cells generated from human CD271(+) bone marrow mononuclear cells. J Transl Med 13:315. https://doi.org/10.1186/s12967-015-0676-9 CrossRefPubMedPubMedCentralGoogle Scholar
- 29.Liu M, Chen F, Sha L, Wang S, Tao L, Yao L, He M, Yao Z, Liu H, Zhu Z, Zhang Z, Zheng Z, Sha X, Wei M (2014) (−)-Epigallocatechin-3-gallate ameliorates learning and memory deficits by adjusting the balance of TrkA/p75NTR signaling in APP/PS1 transgenic mice. Mol Neurobiol 49:1350–1363. https://doi.org/10.1007/s12035-013-8608-2 CrossRefPubMedGoogle Scholar
- 37.Sarkar A, Tatlidede S, Scherer SS, Orgill DP, Berthiaume F (2011) Combination of stromal cell-derived factor-1 and collagen-glycosaminoglycan scaffold delays contraction and accelerates reepithelialization of dermal wounds in wild-type mice. Wound Repair Regen 19:71–79. https://doi.org/10.1111/j.1524-475X.2010.00646.x CrossRefPubMedGoogle Scholar
- 40.Truzzi F, Marconi A, Atzei P, Panza MC, Lotti R, Dallaglio K, Tiberio R, Palazzo E, Vaschieri C, Pincelli C (2011) p75 neurotrophin receptor mediates apoptosis in transit-amplifying cells and its overexpression restores cell death in psoriatic keratinocytes. Cell Death Differ 18:948–958. https://doi.org/10.1038/cdd.2010.162 CrossRefPubMedGoogle Scholar
- 41.Truzzi F, Saltari A, Palazzo E, Lotti R, Petrachi T, Dallaglio K, Gemelli C, Grisendi G, Dominici M, Pincelli C, Marconi A (2015) CD271 mediates stem cells to early progeny transition in human epidermis. J Invest Dermatol 135:786–795. https://doi.org/10.1038/jid.2014.454 CrossRefPubMedGoogle Scholar
- 42.Wang T, Takikawa Y, Watanabe A, Kakisaka K, Oikawa K, Miyamoto Y, Suzuki K (2014) Proliferation of mouse liver stem/progenitor cells induced by plasma from patients with acute liver failure is modulated by P2Y2 receptor-mediated JNK activation. J Gastroenterol 49:1557–1566. https://doi.org/10.1007/s00535-013-0927-6 CrossRefPubMedGoogle Scholar
- 45.Zhang M, Sun L, Wang X, Chen S, Kong Y, Liu N, Chen Y, Jia Q, Zhang L, Zhang L (2014) Activin B promotes BMSC-mediated cutaneous wound healing by regulating cell migration via the JNK-ERK signaling pathway. Cell Transplant 23:1061–1073. https://doi.org/10.3727/096368913x666999 CrossRefPubMedGoogle Scholar
- 46.Zhang M, Cao Y, Li X, Hu L, Taieb SK, Zhu X, Zhang J, Feng Y, Zhao R, Wang M, Xue W, Yang Z, Wang Y (2018) Cd271 mediates proliferation and differentiation of epidermal stem cells to support cutaneous burn wound healing. Cell Tissue Res 371:273–282. https://doi.org/10.1007/s00441-017-2723-8 CrossRefPubMedGoogle Scholar