Role of Trichocytic Keratins in Anti‐Neuroinflammatory Effects After Spinal Cord Injury

Shifting microglia/macrophages to M2 anti‐inflammatory phenotype is considered a pivotal therapeutic target for spinal cord injury (SCI). Keratin extracted from human hair exhibits anti‐inflammatory properties. However, the differences among the 17 types of human hair keratins and their mechanisms of anti‐inflammation remain poorly understood. In this study, the anti‐inflammatory activity of 17 human hair keratins using a recombinant synthesis approach is explored. Distinct activities of microglia/macrophage phenotype modulation of 17 keratins are found through qRT‐PCR analysis, and recombinant keratin 33A (RK33A) and RK35 display superior anti‐inflammatory efficiency compared to other keratins. Immunofluorescence and flow cytometry reveals a significant effect of RK33A on the regulation of microglia/macrophages into an anti‐inflammatory M2 phenotype. Subsequently, recombinant keratin 33A nanofiber (RKNF33A) is fabricated to evaluate its in vivo anti‐inflammatory and nerve regeneration properties using the rat T9 spinal cord lateral hemisection model. The optimized keratin‐based nanofiber shows outstanding performance in enhancing M2 polarization, reducing glial scarring, promoting nerve regeneration, and improving locomotor function recovery in SCI rats. Moreover, it is preliminarily found that RK33A regulates M2 microglia/macrophage polarization by upregulating the PI3K/AKT/mTOR signaling pathway. Together, this study reveals that trichocytic keratins exhibit distinct anti‐inflammatory properties, providing a prospective treatment for SCI by modulating microglia/macrophage polarization.

• Publication year

  2023

• Venue

  Advanced Functional Materials

• Publication date

  2023-03-15

• Fields of study

  Not labeled

• Identifiers
  DOI 10.1002/adfm.202212870
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar

• No claims are published for this paper.

• No concepts are published for this paper.

• Nerve Growth Factor-Laden Anisotropic Silk Nanofiber Hydrogels to Regulate Neuronal/Astroglial Differentiation for Scarless Spinal Cord Repair.

  2022cited by this paper
• The PI3K/AKT signalling pathway in inflammation, cell death and glial scar formation after traumatic spinal cord injury: Mechanisms and therapeutic opportunities

  2022cited by this paper
• Atractylenolide III ameliorates spinal cord injury in rats by modulating microglial/macrophage polarization

  2022cited by this paper
• Role of Inflammation in Traumatic Brain Injury-Associated Risk for Neuropsychiatric Disorders: State of the Evidence and Where Do We Go From Here.

  2021cited by this paper
• Engineering spinal cord repair.

  2021cited by this paper
• Fabrication of ulcer-adhesive oral keratin hydrogel for gastric ulcer healing in a rat

  2021cited by this paper
• M2 macrophages, but not M1 macrophages, support megakaryopoiesis by upregulating PI3K-AKT pathway activity

  2021cited by this paper
• Mechanotransduction via the coordinated actions of integrins, PI3K signaling and Connexin hemichannels

  2021cited by this paper
• Inflammation after spinal cord injury: a review of the critical timeline of signaling cues and cellular infiltration

  2021cited by this paper
• Study of Mechanisms of Recombinant Keratin Solubilization with Enhanced Wound Healing Capability

  2020cited by this paper
• A novel hydrogel-based treatment for complete transection spinal cord injury repair is driven by microglia/macrophages repopulation.

  2020cited by this paper
• Construction of injectable silk fibroin/polydopamine hydrogel for treatment of spinal cord injury

  2020cited by this paper
• Microenvironment-responsive immunoregulatory electrospun fibers for promoting nerve function recovery

  2020cited by this paper
• Neurotrophin-3-Loaded Multichannel Nanofibrous Scaffolds Promoted Anti-Inflammation, Neuronal Differentiation, and Functional Recovery after Spinal Cord Injury.

  2020cited by this paper
• Polymer scaffolds facilitate spinal cord injury repair.

  2019cited by this paper
• Human Hair Keratin Hydrogels Alleviate Rebleeding after Intracerebral Hemorrhage in a Rat Model.

  2019cited by this paper
• The origin, fate, and contribution of macrophages to spinal cord injury pathology

  2019cited by this paper
• The translational landscape in spinal cord injury: focus on neuroplasticity and regeneration

  2019cited by this paper
• Spinal cord repair: advances in biology and technology

  2019cited by this paper
• Recombinant Human Hair Keratin Nanoparticles Accelerate Dermal Wound Healing.

  2019cited by this paper
• Multifunctionalized hydrogels foster hNSC maturation in 3D cultures and neural regeneration in spinal cord injuries

  2019cited by this paper
• Keratin biomaterials augment anti-inflammatory macrophage phenotype in vitro.

  2018cited by this paper
• Recombinant human hair keratin proteins for halting bleeding

  2018cited by this paper
• An in vitro study of non-aligned or aligned electrospun poly(methyl methacrylate) nanofibers as primary rat astrocytes-loading scaffold.

  2018cited by this paper
• 3D Printed Stem‐Cell Derived Neural Progenitors Generate Spinal Cord Scaffolds

  2018cited by this paper
• Bioinspired Hydrogel Electrospun Fibers for Spinal Cord Regeneration

  2018cited by this paper
• Traumatic spinal cord injury

  2017cited by this paper
• Combinatorial Therapies After Spinal Cord Injury: How Can Biomaterials Help?

  2017cited by this paper
• Current Options for Cell Therapy in Spinal Cord Injury.

  2017cited by this paper
• Physical chitosan microhydrogels as scaffolds for spinal cord injury restoration and axon regeneration.

  2017cited by this paper
• Enabling Technologies for Cell-Based Clinical Translation Concise Review : Bridging the Gap : Novel Neuroregenerative andNeuroprotective Strategies in Spinal Cord Injury

  2016cited by this paper
• Development and assessment of kerateine nanoparticles for use as a hemostatic agent.

  2016cited by this paper
• Aligned PLLA nanofibrous scaffolds coated with graphene oxide for promoting neural cell growth.

  2016cited by this paper
• Mechano-Transduction Signals Derived from Self-Assembling Peptide Nanofibers Containing Long Motif of Laminin Influence Neurogenesis in In-Vitro and In-Vivo

  2016cited by this paper
• Graft of the NT-3 persistent delivery gelatin sponge scaffold promotes axon regeneration, attenuates inflammation, and induces cell migration in rat and canine with spinal cord injury.

  2016cited by this paper
• Control of macrophage metabolism and activation by mTOR and Akt signaling.

  2015cited by this paper
• Directed neurite growth of rat dorsal root ganglion neurons and increased colocalization with Schwann cells on aligned poly(methyl methacrylate) electrospun nanofibers.

  2014cited by this paper
• In vitro response of macrophage polarization to a keratin biomaterial.

  2014cited by this paper
• Elastic three‐dimensional poly (ε‐caprolactone) nanofibre scaffold enhances migration, proliferation and osteogenic differentiation of mesenchymal stem cells

  2013cited by this paper
• Hemostatic properties and the role of cell receptor recognition in human hair keratin protein hydrogels.

  2013cited by this paper
• Rapamycin unbalances the polarization of human macrophages to M1

  2013cited by this paper
• Repertoire of microglial and macrophage responses after spinal cord injury

  2011cited by this paper
• Alternative activation of macrophages by IL‐4 requires SHIP degradation

  2011cited by this paper
• Robust CNS regeneration after complete spinal cord transection using aligned poly-L-lactic acid microfibers.

  2011cited by this paper
• A Review of Keratin-Based Biomaterials for Biomedical Applications

  2010cited by this paper
• Targeting the phosphoinositide 3-kinase pathway in cancer

  2009cited by this paper
• Films based on human hair keratin as substrates for cell culture and tissue engineering.

  2009cited by this paper
• A generic protocol for the expression and purification of recombinant proteins in Escherichia coli using a combinatorial His6-maltose binding protein fusion tag

  2007cited by this paper

• A novel natural protein modulates foam macrophage formation: Implications for spinal cord injury intervention

  2025cites this paper
• Recombinant Keratin: Comprehensive Review of Synthesis, Hierarchical Assembly, Properties, and Applications.

  2025cites this paper
• Self‐Enhancing Drug Pair‐Driven Selenium Nanotherapeutics Reverses Microglial Pyroptosis Through NLRP3/Caspase‐1 Pathway and Neuronal Apoptosis for Treatment of Spinal Cord Injury

  2025cites this paper
• Mechanism-guided rational design of anti-neuroinflammatory keratin-derived protein for spinal cord injury repair

  2025cites this paper
• Chiral Nanoagonist Targeting EGFR for Nerve Injury Repair

  2025cites this paper
• An Integrated Modular Vaccination System for Spatiotemporally Separated Perioperative Cancer Immunotherapy

  2025cites this paper
• Bisphosphonates activated keratin assembled nanoparticle targeting bone fracture for enhanced immunomodulatory and osteoinductivity

  2024cites this paper
• Engineered keratin/bFGF hydrogel to promote diabetic wound healing in rats.

  2024cites this paper
• An esterase-activatable nanoprodrug mitigates severe spinal cord injury via alleviating ferroptosis and reprogramming inflammatory microenvironment

  2024cites this paper
• Functional Polyphenol-Based Nanoparticles Boosted the Neuroprotective Effect of Riluzole for Acute Spinal Cord Injury.

  2024cites this paper
• Rational Design of Human Hair Keratin−Driven Proteins for Hair Growth Promotion

  2024cites this paper
• Recent advances in preparation and biomedical applications of keratin based biomaterials

  2024cites this paper
• In Situ Detection of Neuroinflammation Using Multicellular 3D Neurovascular‐Unit‐on‐a‐Chip

  2023cites this paper
• TREM2 mitigates NLRP3-mediated neuroinflammation through the NF-κB and PI3k/Akt signaling pathways in juvenile rats exposed to ambient particulate matter

  2023cites this paper
• Rational design of water‐soluble, homotypic keratins self‐assembly with enhanced bioactivities

  2023cites this paper
• Robust and Multifunctional Nanoparticles Assembled from Natural Polyphenols and Metformin for Efficient Spinal Cord Regeneration.

  2023cites this paper
• Cellular Mechanisms Driving the Distinct Behavior of Trichocyte Keratins in Wound Healing

  2023cites this paper