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Macrophage and Its Role in Wound Healing
Local immune cells include resident macrophages that activate their hosts and help them engage in healing. In their article, Koh and DiPietro study the process of wound recovery with maximum attention being paid to the inflammatory response of these cells (1). Neutrophils arrive as the dominant components infiltrating open wounds; at earlier stages of repair, macrophages deal with acute inflammatory conditions by removing the given infiltrators (Koh and DiPietro 2). At the final stage, T lymphocytes appear to start the process of remodeling and initiate scar formation. The authors emphasize that macrophages participate in all repair phases and can influence those (Koh and DiPietro 3). The experiments conducted by the researchers have shown that wounds depleted of macrophages demonstrated delayed wound closure and decreased collagen synthesis. Without the mediators and cytokines, these cells produce the process of recovery tends to last for longer.
The study suggests that macrophages can transit from a pro-inflammatory to reparative or alternative phenotype; the latter is characterized by the switch from inflammation to the proliferation of cells in a healing wound. As the researchers indicate, “M1 microphages are induced to develop into a novel M2-like phenotype via an IL-4/IL-13-independent manner” (Koh and DiPietro 4). The findings show that the M1 phenotype is mostly present at earlier repair stages, while M2-like analog occurs during its later phases. Macrophages can influence the healing process through the production of proteases stimulating ECM synthesis and fostering remodeling. With regards to the fact that six million US citizens suffer from inadequate wound healing, the use of these enzymes in regenerative medicine could be a means to effectively resolve the situation (Koh and DiPietro 6). The study suggests that the same strategy is recommended to treat patients with diabetes and those of senior age.
Mesenchymal Stem Cell Activities Mediated by GPNMB
The area of regenerative medicine faced a significant professional leap after MSC-based therapy has been introduced. A range of clinical studies has proven that MSCs possess immense therapeutic potential in matters of tissue repair (Yu et al. 1511). As the scholars admit, “systemic delivery of MSCs may reduce the numbers of cells that finally appear at target sites due to being trapped and relocated within lung, liver, and spleen (Yu et al. 1511). A notable fact about these cells is that depending on a surrounding inflammatory milieu, which they inhabit, their functional activities may either show faster or slower dynamics. The given dependency often determines how a subsequent tissue healing will flow and what the overall recovery rate will be. It is also indicated in the article that macrophages play a relevant part in inflammation and wound repair too (Yu et al. 1511). The researchers, however, argue that interactions between MSCs and macrophages require further study.
GPNMB, which is expressed in multiple cells, carries the function of an adhesion molecule or a cell surface receptor. According to the data provided by Yu et al., loss of GPNMB is usually associated with reduced tissue healing (1512). With regards to this fact, the authors hypothesize that OA/GPNMB serves as a potential mediator of MSCs function (Yu et al. 1512). To test their theory, the researchers use TRIzol reagent and a variety of antibodies including anti-CD86 allophycocyanin and anti-CD44 APC to isolate total RNA from cultural cells. During the experiments, the environmental temperature was kept at 37°C; all reactions were repeated three times for higher accuracy. The results have shown that “OA/GPNMB stimulates osteogenic differentiation of MSCs in a dose dependent manner” (Yu et al. 1514). Considering the research findings, GPNMB arrives as a critical factor to promote proliferative and migratory activities of MSCs.
GPNMB and Cancer
Recent studies have discovered that GPNMB (a type 1 transmembrane protein) has an inhibitory role in some cancers. As Taya and Hammes indicate in their article, while glycoprotein possesses tumor suppressor properties valid for breast cancer, it, at the same time, can cause metastasis development in other disease types (2). It is currently known that GPNMB is highly expressed in a variety of tumors including melanoma, carcinoma, prostate cancer, and more (Taya and Hammes 2). Considering the multifaceted nature of this particular protein, it has certain vital domains tending to regulate cell-to-cell migration and cell growth. The authors point out that due to this unique property GPNMB can influence the plasma membrane expression (Taya and Hammes 3). In the case the leucine residues start to mutate, the ferment creates a favorable environment for the process to develop.
GPNMB expression is often associated with increased invasion, migration, and proliferation of tumor cells. The researchers stress out that this protein can promote a wide range of processes including cell differentiation and adhesion that is normally observed in metastasis (Taya and Hammes 4). Its role as a driver of primary tumor growth is strongly emphasized in the article. As seen from the data, “GPNMB is found in the tumor-epithelium of approximately 10% of human breast cancers and in the stroma of nearly 70% of breast cancers” (Taya and Hammes 4). The experiments on mice have demonstrated that ferment injections stimulated aggressive behavior of tumor cells forcing them to proliferate. In the meantime, silencing GPNMB helped to significantly reduce the proliferation rate. The pro-tumorigenic effect of GPNMB is primarily attributed to its ability to interact with integrins, augment epithelial-mesenchymal transition (EMT), and activate matrix metalloproteinases (MMPs).
The present paper has examined the biological roles of macrophages and GPNMB, as well as their influence on cells by reviewing the three scholarly articles listed on a reference page. As referred to macrophage, the sphere of medicine defines it as a prominent inflammatory cell, which fulfills host defensive functions through engaging in wound repair. Its activity is tracked throughout all stages of a wound healing process. Glycoprotein non-metastatic melanoma protein B (GPNMB), participating in the macrophage-induced mesenchymal stem cells (MSCs) activity, performs the roles of a cell surface receptor and potential mediator of MSCs function mainly. However, it has been proven by recent studies that despite vivid disease-curing properties, GPNMB arrives as a tumor-promoter, which sometimes stimulates aggressive behavior of cancer cells forcing them to invade the body, and proliferate.
The research findings have demonstrated that depleting macrophages from organisms results in the decreased synthesis of collagen and delayed wound closure. The same effect occurs when the loss of GPNMB is observed: the researchers report reduced tissue healing conditioned by the lack of the required mediators. In the meantime, excessive presence of GPNMB in the plasma membrane can stimulate faster mutation of cells and foster their proliferation, which, in turn, may cause tumor growth and further development of cancer. The process usually flows faster if the protein starts to interact with integrins and activate MMPs.
Koh, Timothy J., and Luisa Ann DiPietro. “Inflammation and Wound Healing: The Role of the Macrophage.” Expert Reviews in Molecular Medicine, vol. 13, 2011, pp. 1-14.
Taya, Manisha, and Stephen R. Hammes. “Glycoprotein Non-Metastatic Melanoma Protein B (GPNMB) and Cancer: A Novel Potential Therapeutic Target.” Steroids, vol. 133, 2018, pp. 1-14.
Yu, Bing, et al. “Macrophage‐Associated Osteoactivin/GPNMB Mediates Mesenchymal Stem Cell Survival, Proliferation, and Migration Via a CD44‐Dependent Mechanism.” Journal of Cellular Biochemistry, vol. 117, no. 7, 2016, pp. 1511-1521.