Scientific Explanation of Keratins and Vimentin
1. General Characterization
Structural proteins are integral components of the cellular framework, providing mechanical support, stability, and structure to cells and tissues. Among the most well-known structural proteins are Keratins and Vimentin, both of which play essential roles in maintaining cellular integrity and tissue homeostasis. These proteins not only contribute to the structural framework of cells but also have functional roles in cellular processes such as migration, wound healing, and immune modulation.
Keratins are the primary structural proteins of epithelial cells, forming a resilient scaffold in skin, hair, and the lining of internal organs. Vimentin, on the other hand, is a type of intermediate filament protein found predominantly in mesenchymal cells, playing a crucial role in maintaining cellular flexibility and integrity under stress conditions. Both proteins are essential for the health and function of epithelial and connective tissues, including in the gut.1,2
2. Structure
Keratins are a diverse family of fibrous proteins characterized by their alpha-helical coiled structure. These proteins are divided into two major categories: type I (acidic) and type II (basic) keratins. Keratin filaments are formed by the pairing of type I and type II keratins, creating a strong, insoluble matrix that provides mechanical stability to epithelial cells. Keratin filaments are key components of the cytoskeleton, reinforcing cellular shape and protecting against mechanical damage.1
Vimentin is another critical structural protein, belonging to the intermediate filament family. Its structure features an extended alpha-helical domain that allows it to form filamentous networks within cells, providing elasticity and tensile strength. Vimentin is essential for maintaining the shape and structural integrity of mesenchymal cells and is particularly important in cells that undergo deformation, such as those involved in wound healing or immune responses.2
3. Function
In addition to their structural roles, Keratins and Vimentin play vital roles in cellular defense mechanisms, particularly in response to stress, injury, and inflammation. As a key player in the regulation of cellular movement and immune responses, Vimentin is actively involved in processes like wound healing and immune cell activation. Additionally, Vimentin participate in regulating the immune response by interacting with cytokines and promoting immune cell motility.3
Keratins, especially those found in the epithelial lining of the gut and skin, serve as a protective barrier against pathogens and mechanical stress. In the gut, keratins are involved in maintaining the integrity of the epithelial barrier, which is crucial for preventing bacterial translocation and maintaining immune homeostasis. In response to cellular injury or inflammation, keratin filaments reorganize to facilitate wound healing and epithelial repair.4,5
4. Immune modulating Mechanisms
Structural proteins like Keratins contribute to controlling inflammation through several pathways. Keratins, particularly keratin-8 and keratin-18, have been shown to play anti-inflammatory roles by modulating immune responses in epithelial cells. Keratins act as sensors of cellular stress, and during inflammation, they undergo phosphorylation and reorganization, which aids in protecting cells from damage caused by pro-inflammatory stimuli. Studies have demonstrated that keratin-deficient epithelial cells are more susceptible to inflammation, highlighting their protective role against chronic inflammatory conditions like inflammatory bowel disease (IBD).6 Vimentin aids in controlling the migration of immune cells to sites of inflammation, which is crucial for resolving inflammation efficiently. Disruptions in Vimentin function can lead to prolonged inflammatory responses.
5. Gut Health
Structural proteins also have specific roles in maintaining gut health. In the gut, keratins are essential for maintaining the integrity of the epithelial barrier. They protect the lining of the intestines from mechanical stress and pathogen invasion. Disruption in keratin expression can lead to compromised gut barrier function, allowing harmful bacteria and toxins to penetrate the intestinal wall, which can trigger inflammatory responses and contribute to conditions like IBD and leaky gut syndrome. Keratins also support the regeneration of epithelial cells during injury, promoting faster recovery of the gut lining.6,7
Vimentin is highly expressed in fibroblasts and immune cells within the gut. It plays a key role in the repair of damaged tissue by promoting the migration of fibroblasts to injury sites, where they facilitate wound healing and tissue regeneration. Vimentin also supports the structural integrity of the cells that form the intestinal mucosa, helping to preserve the gut barrier function. By regulating immune cell movement and repair processes, Vimentin contributes to the maintenance of gut health and the resolution of gut-related inflammation.8
6. Clinical Significance and Dietary Supplements
The clinical relevance of Keratins and Vimentin lies in their dual roles as structural proteins and modulators of inflammation and tissue repair. Disruptions in keratin expression have been associated with a higher susceptibility to inflammatory diseases such as IBD, while upregulation of Vimentin is linked to enhanced immune responses and efficient wound healing.
Formulations that target these structural proteins provide a novel approach to supporting both physical and immune health, with potential applications in the prevention and management of inflammation-related diseases.
1 Moll R, Divo M, Langbein L. The human keratins: biology and pathology. Histochem Cell Biol. 2008 Jun;129(6):705-33. doi: 10.1007/s00418- 008-0435-6. Epub 2008 May 7. PMID: 18461349; PMCID: PMC2386534.
2 Lowery J., Kuczmarski E.R., Herrmann H., Goldman R.D. (2015) "Intermediate filaments play a pivotal role in regulating cell architecture and function." Journal of Biological Chemistry, 290(28):17145-17153.
3 Ivaska J., Pallari H.M., Nevo J., Eriksson J.E. (2007) "Novel functions of vimentin as an intracellular and extracellular regulator of cell adhesion, motility, and signaling." Experimental Cell Research, 313(10):2050-2062.
4 Zhong, Wenjie, et al. “Role of Trichocytic Keratins in Anti-Neuroinflammatory Effects After Spinal Cord Injury” Advanced Functional Materials, Volume 33, Issue 23 https://doi.org/10.1002/adfm.202212870.
5 Michele Waters, Pamela VandeVord, Mark Van Dyke, Keratin biomaterials augment anti-inflammatory macrophage phenotype in vitro, Acta Biomaterialia, Volume 66, 2018, Pages 213-223, ISSN 1742-7061, https://doi.org/10.1016/j.actbio.2017.10.042.
6 Liu C, Liu ED, Meng YX, Dong XM, Bi YL, Wu HW, Jin YC, Zhao K, Li JJ, Yu M, Zhan YQ, Chen H, Ge CH, Yang XM, Li CY. Keratin 8 reduces colonic permeability and maintains gut microbiota homeostasis, protecting against colitis and colitis-associated tumorigenesis. Oncotarget. 2017 May 27;8(57):96774-96790. doi: 10.18632/oncotarget.18241. PMID: 29228570; PMCID: PMC5722522.
7 Helenius T.O., Misiorek J.O., Nyström J.H., Fortelius L.E., Habtezion A., Liao J., Asghar M.N., Zhang H., Azhar S., Omary M.B., Toivola D.M. (2016) "Keratin 8 deletion accelerates progression of chemically induced colitis in mice." Journal of Cell Science, 129(18):3452-3463.
8 Lowery J., Kuczmarski E.R., Herrmann H., Goldman R.D. (2015) "Intermediate filaments play a pivotal role in regulating cell architecture and function." Journal of Biological Chemistry, 290(28):17145-17153.