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A Novel Protein Therapy For Efficient Skin Wound

Introduction - A Novel Protein Therapy For Efficient Skin Wound

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Proteins are made up of amino acids these are mainly the “building block” consisting of the amino acids. These amino acids are used in the body to repair muscles and bones and help in the making of hormones and enzymes. Therefore, the researcher put effort into finding a route to heal the wound by the use of protein in the biological process. In the wound repair mechanisms mainly during the proliferative phase collagen deposition plays a crucial role in increasing the wound’s tensile strength. There is a novel protein that is Agrin, which is considered very promising in the case of wound healing therapy. It has been seen that the protein has the character of wound repair if triggered when a tissue is injured therefore there is hope of developing the Agrin protein therapy in case of serious wounds such as wounds due to diabetes and in case of burning wounds.

Research article

Article 1

The main aim of this article is to find out a novel protein therapy that helps in wound healing therapy, mainly in the case of a serious wound that comes from burning or that happens in the diabetes patient, as the wound healing is a complicated and highly arranged biological program that restores the damaged tissue structure (Chakraborty et al. 2021). 

The epithelial wound healing mainly involves the rearrangement or re-establishment of the extracellular matrix of the cell on the skin. In this case, the ECM components help the information of a new stroma, which then supports and inhibit the process of epithelization in the keratinocytes to facilitate wound healing and thus the closing of the wound. In this study, in the migratory cells by analyzing the mRNA and protein levels it has been seen that the expression of Agrin protein shows an increase of about 2 to 4 fold after a wound across the keratinocytes and the fibroblasts. This protein plays a critical role in wound healing.

The breakdown of the ECM is the extracellular matrix, which is an important component in the tissue healing and scar formation procedure case of the tissue healing mechanism. AGRN (that is the Agrin protein) that is a proteoglycan is increased in the skin cells' lining in post-wounding situations. In this case, of wound healing, the first aim is to focus on the early phase of the wound healing operation when the re-epithelialization is marked by the keratinocytes. Agrin is a protein that is signed by a wound, which is an ECM or extracellular matrix protein, which is enhanced in the wounded cells when compared with the unwounded cells (Chakraborty et al. 2021). It is seen in this study that the le4vel of agrin was upregulated during the early phase of the wound healing system within which the wound coverage was initiated by a level of mRNA and proteins in the migratory cells within a times period of 24hours during the wound-healing phase. During this mechanism of wound healing, during the mechanism of the wound healing, the agrin’s increased expression was seen. In the keratinocytes HaCat and HEK within a time of 3 to 24 hours, the expansion has been seen. In this case, there were no changes in the hypodermis and in dermal-white adipose tissues during the increase in the agrin expression in the injured layer of the dermis (Chakraborty et al. 2021). The result shows the increase in the expression of the Argin protein during the early phase of wound healing and it does not affect other neighbor tissues in this mechanism therefore the trigger in the expression of Argin plays a very important role in the process of wound healing.

Article 2

The aim of this study is to focus on the cytocompatible and biodegradable fibrous wound healing mechanism by the electro spinning protein of plant and animal.

The wound healing delay and chronic wound is a burden for the medical field. Wound healing mechanism is a complex biological system, which creates extra complication I the patients’ condition. The research on the wound healing mechanisms shows interest manly on the electrospinning wound dressing with nano protein fiber. This method defines a number of characters and the properties that support and help in the accelerating wound healing. They show a physical barrier and physical protection exhibiting a greater surface area resembling the structure of the extracellular matrix that is ECM. In this case some antimicrobial agents also can be attached with the fibres also to avoid any microbial infection (Akhmetova et al. 2020). Although it shows the potential affectivity in case of wound healing by the nano fiber delivery from the plant and animal protein there are many challenges in the application of this process I case of skin wound healing as it is dependent o the source of animal and plan protein.

Article 3

Protein is the main component of the tissue, which is made up of a “building block” of many amino acids molecules therefore in case of the wound the ECM, get affected. The article mainly aims on the healing of the skin by the therapy with application of polypeptide-protein hydrogel (Cheng et al. 2020).

This article shows that in this protein hydrogel system the Ag + not only works on cross linking providing a microenvironment but also can provide the access of K2(SL)6K2 (KK)” polypeptide, this peptide then acts on endowsing the hydrogel property. In the in vivo technique it has been seen that the ability of collagen deposition and vascularization process result in the generation of new tissue on the place of wound in the early stage of the wound healing mechanism (Cheng et al. 2020). This method of wound healing promises a great area in the biomedical field although the Agrin protein therapy shows more promising area of interest I case of serious and chronic wound y the urn or a severe cut.

Mass media

Wound healing is considered to be a natural biological process and it is achieved in four very precise as well as highly programmed stages. The very first stage of wound healing is “homeostasis”, “inflammation”, “proliferation”, as well as “remodelling”. The homeostasis phase consists of vascular constriction and platelet aggregation along with degranulation. The same fibrin formation takes place that helps to make the homeostatic environment for wound healing. On the other hand, in the inflammation phase, at first infiltration of neutrophils takes place. Other than neutrophil, monocyte and lymphocyte infiltration also take place. Differentiation of monocyte to macrophage takes place that is primarily responsible for inflammation in the damaged area. The next stage is proliferation where “re-epithelialization”, “collagen synthesis”, “angiogenesis”, and “ECM formation” occur. In the last phase of Remodelling, collagen modelling takes place. At the same time, vascular maturation as well as regression occurs.

Aim

The aim of the mass media papers is to analyse a novel protein that is used in wound-healing therapy. In this regard, three online articles will be searched to find out the best and most efficient protein therapy that can help in the healing of chronic wounds.

Findings

Agrin is a protein that has been recently discovered that helps in the promotion of wound healing and skin repairing. Therefore, it can be stated that Agrin therapy is considered a new pave for chronic wound healing. It has been found that Agrin, which is originally a proteoglycan, is implanted in the microenvironment of the wound it helps in the efficient healing of the wound. The result of a mass media paper has shown that epithelial healing of the wound is directly influenced by the reconstruction of the lost “Extracellular Matrix” components that can help to generate a new stroma. This helps in supporting the re-epithelization of keratinocytes accelerating wound healing (Nature, 2021). Agrin is one of the ECM proteins that are present in higher amounts in the damaged parts of the skin. 

According to a peer-review news article in Singapore, Agrin protein that is released after a skin injury helps in healing the wound and it is found to be the most efficient in this case. It mainly acts at the proliferation stage of wound healing which is the third stage. Other than the skin, it is effective in wound healing of tissues as well as organs (Eurekalert, 2021). The researchers also claimed that this protein therapy is most beneficial for diabetic patients and for others who have burned severely. In comparison with collagen wound healing model, use of agrin protein accelerates wound healing process. Besides this, it preserves microenvironment at healing site, which induces better repairing mechanism.

Agrin is considered the most potent protein that accelerates wound healing and this is done by the “Hippo-Yap signalling”. Yap1 is found in limbal stem cell nuclei as well as nuclei of TACs and actively helps in the activation of the Agrin protein. From this article, it has also been found that Agrin plays an important role on myocardial infarction as well.

Critical analysis

It has been found that during the healing of the skin, Agrin levels are consistently enhanced by 2-4 times within 24 hours post-wound phase. In the keratinocytes and fibroblast cells, Agrin levels enhance; however, if comparing the levels of this enhancement, keratinocytes have shown to have more levels of Agrin. Therefore, the genes that produce agrin in the cells can be isolated with the use of restriction endonuclease enzyme and ligase enzyme; this gene can be implemented within the plasmid of a host cell such as yeast to yield higher levels of in-vitro Agrin protein. In this way, this protein can be used as protein therapy in wound healing. This article further found that if the Agrin is depleted in the skin that impairs the wound healing. The researchers utilized “three independent stealth siRNAs” in order to delete the Agrin and then conducted a punch-biopsy to see the effect of Agrin protein depletion. Therefore, it can be stated that Agrin protein therapy is considered to be an effective way to accelerate wound healing. Furthermore, the researchers of the news article also showed that if an exogenous supplement of this protein is given to any person it promotes the healing of injured skin. Further, human, as well as pre-clinical models showed if aunty type of physical injury occurs to the skin, expression of Agrin is significantly enhanced and that helps in the preservation of mechanical architecture of injured skin.

Another research article has found the same result as the previous articles. Agrin has been found to promote the proliferation of stem cells when experimented with in-vitro. It has been found to accelerate the rate of wound healing in the corneal epithelium by activating the proliferation of limbal cells. dephosphorylation of “Yap1” is the mechanism by which the nuclear translocation of Yap1 occurs (Arvojournals, 2020). Other than that, translocation as well as expression of “Cyclin D1” occurs that in turn promote the proliferation of “limbal stem cells”.

Conclusion

From the overall evaluation, it can be conclusively stated that the novel protein therapy is also the most effective and efficient aspect for skin wounds. However, it can be also stated that for the evaluation of this topic some of the major analysis has been done here. Moreover, for evaluating this topic, major aims and objectives and critical analysis have been evaluated here. Agrin protein can be used as protein therapy in wound healing. This article helps in finding some of the major aspects that the Agrin is depleted in the skin that impairs wound healing. Apart from this, it has been also stated that the protein has the character of wound repair if triggered when a tissue is injured therefore there is the hope of developing the Agrin protein therapy in case of serious wounds such as wounds due to diabetes and in case of burning wounds. Therefore, it can be stated that Agrin protein therapy is considered an effective way to accelerate wound healing. From this evaluation, it can be also stated that Agrin protein shows an increase of about 2 to 4 fold after a wound across the keratinocytes and the fibroblasts. This protein plays a critical role in wound healing.

References

Akhmetova, A. and Heinz, A., 2020. Electrospinning proteins for wound healing purposes: Opportunities and challenges. Pharmaceutics13(1), p.4.

Arvojournals, 2020.Agrin Promotes Limbal Stem Cell Proliferation and Corneal Wound Healing Through Hippo-Yap Signaling Pathway. https://iovs.arvojournals.org/article.aspx?articleid=2766077

Chakraborty, S., Sampath, D., Yu Lin, M.O., Bilton, M., Huang, C.K., Nai, M.H., Njah, K., Goy, P.A., Wang, C.C., Guccione, E. and Lim, C.T., 2021.Agrin-Matrix Metalloproteinase-12 axis confers a mechanically competent microenvironment in skin wound healing. Nature communications, 12(1), pp.1-18.

Cheng, L., Cai, Z., Ye, T., Yu, X., Chen, Z., Yan, Y., Qi, J., Wang, L., Liu, Z., Cui, W. and Deng, L., 2020. Injectable polypeptide?protein hydrogels for promoting infected wound healing. Advanced Functional Materials30(25), p.2001196.

Eurekalert, 2021. A novel protein therapy for efficient skin wound healing. https://www.eurekalert.org/news-releases/936968

Larouche, J., Sheoran, S., Maruyama, K. and Martino, M.M., 2018. Immune regulation of skin wound healing: mechanisms and novel therapeutic targets. Advances in wound care7(7), pp.209-231.

Nature, 2021.Agrin-Matrix Metalloproteinase-12 axis confers a mechanically competent microenvironment in skin wound healing. https://www.nature.com/articles/s41467-021-26717-7

Tottoli, E.M., Dorati, R., Genta, I., Chiesa, E., Pisani, S. and Conti, B., 2020. Skin wound healing process and new emerging technologies for skin wound care and regeneration. Pharmaceutics12(8), p.735.

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