Keratocytes, the resident cells of the corneal stroma, are responsible for maintaining turnover of this tissue by synthesizing extracellular matrix components. When the cornea is injured, the keratocytes migrate to the wounded site and participate in the stromal wound healing. The neuropeptide substance P (SP), which is also known to be produced by non-neuronal cells, has previously been implicated in epithelial wound healing after corneal injury. Corneal scarring, which occurs in the stroma when the process of wound healing has malfunctioned, is one of the major causes of preventable blindness. This study aimed to elucidate the potential role of SP in keratocyte migration and therefore in stromal wound healing. We report that the expression and secretion of SP in human keratocytes are increased in response to injury in vitro. Moreover, SP enhances the migration of keratocytes by inducing the actin cytoskeleton reorganization and focal adhesion formation through the activation of the phosphatidylinositide 3-kinase and Ras-related C3 botulinum toxin substrate 1/Ras homolog gene family, member A pathway. Furthermore, SP stimulation leads to upregulated expression of the proinflammatory and chemotactic cytokine interleukin-8 (IL-8), which also contributes significantly to SP-enhanced keratocyte migration and is able to attract neutrophils. In addition, the preferred SP receptor, the neurokinin-1 receptor, is necessary to induce keratocyte migration and IL-8 secretion. In conclusion, we describe new mechanisms by which SP enhances migration of keratocytes and recruits neutrophils, two necessary steps in the corneal wound-healing process, which are also likely to occur in other tissue injuries.
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http://dx.doi.org/10.1124/mol.115.101014 | DOI Listing |
FASEB J
December 2024
Department of Medical and Translational Biology, Umeå University, Umeå, Sweden.
Ophthalmol Ther
November 2024
Dr. Rolf M. Schwiete Center for Limbal Stem Cell and Congenital Aniridia Research, Saarland University, Kirrberger Str. 100, Homburg, Saarland, 66424, Germany.
Introduction: In congenital aniridia caused by mutations in paired box 6 (PAX6), PAX6 influences the migration and differentiation of limbal epithelial cells (LECs), thereby playing a pivotal role in aniridia-associated keratopathy. The antidepressants ritanserin and duloxetine affect PAX6 expression in LECs. Limbal stromal cells, which support limbal epithelial stem cells, are crucial in the limbal stem cell niche.
View Article and Find Full Text PDFEur J Pharmacol
November 2024
Department of Ophthalmology, Shijiazhuang Aier Eye Hospital, Shijiazhuang, 050000, China.
bioRxiv
August 2024
Courant Institute and Department of Biology, New York University, New York, NY 10012.
Motile cells migrate directionally in the electric field in a process known as galvanotaxis, important and under-investigated phenomenon in wound healing and development. We previously reported that individual fish keratocyte cells migrate to the cathode in electric fields, that inhibition of PI3 kinase reverses single cells to the anode, and that large cohesive groups of either unperturbed or PI3K-inhibited cells migrate to the cathode. Here we find that small uninhibited cell groups move to the cathode, while small groups of PI3K-inhibited cells move to the anode.
View Article and Find Full Text PDFJ Funct Biomater
July 2024
Department of Ophthalmology, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390, USA.
In the original publication [...
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