Targeting Microtubules for Wound Repair

Abstract

Significance: Fast and seamless healing is essential for both deep and chronic wounds to restore the skin and protect the body from harmful pathogens. Thus, finding new targets that can both expedite and enhance the repair process without altering the upstream signaling milieu and causing serious side effects can improve the way we treat wounds. Since cell migration is key during the different stages of wound healing, it presents an ideal process and intracellular structural machineries to target. Recent Advances and Critical Issues: The microtubule (MT) cytoskeleton is rising as an important structural and functional regulator of wound healing. MTs have been reported to play different roles in the migration of the various cell types involved in wound healing. Specific microtubule regulatory proteins (MRPs) can be targeted to alter a section or subtype of the MT cytoskeleton and boost or hinder cell motility. However, inhibiting intracellular components can be challenging in vivo, especially using unstable molecules, such as small interfering RNA. Nanoparticles can be used to protect these unstable molecules and topically deliver them to the wound. Utilizing this approach, we recently showed that fidgetin-like 2, an uncharacterized MRP, can be targeted to enhance cell migration and wound healing. Future Directions: To harness the full potential of the current MRP therapeutic targets, studies should test them with different delivery platforms, dosages, and skin models. Screening for new MT effectors that boost cell migration in vivo would also help find new targets for skin repair.Keywords: microtubules, nanoparticle, siRNA, Fidgetin-like 2, cell migration SCOPE AND SIGNIFICANCEThis review explores the role of microtubules (MTs), a major component of the cell's internal skeleton, in wound healing, especially during cell migration. The structure and function of MTs are spatially and temporally regulated by microtubule regulatory proteins (MRPs), which have diverse effects on cell migration depending on their role and the cell type being targeted. The review also presents alternative techniques to identify and examine new therapeutic wound-healing targets. TRANSLATIONAL RELEVANCEWe recently characterized the role of fidgetin-like 2 (FL2), a novel MRP that can be targeted to enhance cell migration and healing both in vitro and in vivo wound-healing models. Identifying other MRPs that are involved in cell migration and wound healing !can elucidate how these proteins function and how they affect cell motility. As a faster and acute alternative to genetically modified animal models, RNA interference (RNAi) can be easily used to deplete these targets directly at the wound sites by utilizing nanotechnology and other technologies to deliver and protect small interfering RNA (siRNA). CLINICAL RELEVANCEBoth chronic and acute wounds are costly and painful medical issues

[Retracted] Identification of the Potential Biomarkers Involved in the Human Oral Mucosal Wound Healing: A Bioinformatic Study

“…Aurora kinase A (AURKA) encodes a cell cycle-regulated kinase that is involved in the formation and/or stabilization of microtubules [45]. Targeting microtubules could potentially enhance the wound healing process by promoting cell migration [46]; thus, AURKA might impact oral mucosa wound repair by influencing cell migration. PLK1 is a family member of the polo-like kinase (Plks) family, which has been demonstrated to be a key regulator of the cell cycle [47].…”

Identification of Trombospondin-1 as a Novel Amelogenin Interactor by Functional Proteomics

“…The interaction of AMEL-2 with protein belonging to the tubulin family may also play a role in wound healing. Although the exact mechanism of tubulin action in this process remains debated, the microtubules dynamics regulates many aspects of cell migration (Ganguly et al, 2012 ; Charafeddine et al, 2016 ).…”

Zebrafish as a Model System to Study the Mechanism of Cutaneous Wound Healing and Drug Discovery: Advantages and Challenges

“…Here, at the injury side, dexamethasone further triggers cell apoptosis and reduces immune modulatory activity and macrophages, indicating delayed wound healing [75]. Likewise, sodium warfarin and hydrocortisone application to cutaneous wounds in zebrafish impair granulation tissue formation and delay the inflammatory phase and the re-epithelialization process [76,77]. This shows that the above-tested drugs are not suitable to be applied directly to cutaneous wounds.…”

“…Microtubules, a major component of the cytoskeleton, are involved in mitosis, cell motility, and the maintenance of cell shape. In wound healing, targeting microtubules early might impact wound repair at the inflammatory and proliferative stages [76]. However, activated neutrophils protect the wound from pathogenic microbe invasion by producing proteases, ROS, and antimicrobial peptides.…”