Sociedade Brasileira para o Desenvolvimento da Pesquisa em Cirurgia - Online version e-ISSN: 1678-2674

Downregulation of the high-mobility protein HMGB1 (amphoterin) induced by overexpression of MFGE8 (lactaderin) improves the prognosis of blunt abdominal injury

Among the functions of the intestinal mucosa, it acts as a barrier that allows the containment of undesirable elements in the intestine while allowing the absorption of nutrients (RIBEIRO et al.,2018).

When there is blunt abdominal injury, this function can be severely impaired, making the intestine a gateway for systemic inflammatory processes, which can rapidly progress to multi-organ dysfunction, leading to life-threatening complications.

In this scenario, understanding the pathogenesis of intestinal damage caused by abdominal trauma is essential to a better prognosis.

In the article Potential influences of expression levels of MFGE8 and HMGB1 on the intestinal mucosal barrier function and inflammatory response after blunt abdominal injury in rats published in Acta Cirúrgica Brasileira, vol. 37, n. 3, researchers from the Department of Trauma Surgery at the First Affiliated Hospital of Wenzhou Medical University, China, present their findings from the analysis of the expression of MFGE8 and HMGB1 proteins in the recovery of intestinal injuries caused by abdominal trauma.

Many studies have already proven the benefits of MFGE8 in recovering injured tissues (BU et al., 2007). The results obtained in the presented article converge with the literature, which attributes the therapeutic effects of MFGE8 overexpression to the negative regulatory effect (downregulation) it exerts on the HMGB1 protein. However, this is just one of the interesting reflections of the complex relationship between these proteins.

Image: Acta Cirúrgica Brasileira

The work developed by the authors seeks to analyze this dynamic only in the context of a blunt abdominal injury that affects the intestinal mucosal barrier. In the presented scenario, it is demonstrated the attenuation of the inflammatory response and a significant improvement in the recovery of the intestinal barrier, thanks to the intravenous intervention with human recombinant MFGE8, reducing the expressive levels of HMGB1.

With a description of the reagents, equipment and technical procedures performed, the study evaluated the RhoA/ROCK signaling pathway (INOUE et al., 2004) in Sprague Dawley (SD) rats, which were submitted to abdominal contusion. Trauma provoked an inflammatory response in intestinal tissues, with increased serum levels of TNF-α, IL-1β, IL-6 and MDA. Upregulation of HMGB1, RhoA and ROCK2 also occurred while MFGE8 showed downregulation. Such effects and the relief provided by the intervention with rhMFGE8 are demonstrated in the article, including the use of figures and tables.

Read more

Ribeiro AB, Giusti H, Souza APT, Franci CR, Saia RS. Dexamethasone prevents lipopolysaccharide-induced epithelial barrier dysfunction in rat ileum. Shock. 2018;49(3):334-344.

Bu HF, Zuo XL, Wang X, Ensslin MA, Koti V, Hsueh W, et al. Milk fat globule-EGF factor 8/lactadherin plays a crucial role in maintenance and repair of murine intestinal epithelium. J Clin Invest. 2007;117(12):3673-83.

Inoue M, Rashid MH, Fujita R, Contos JJ, Chun J, Ueda H. Initiation of neuropathic pain requires lysophosphatidic acid receptor signaling. Nat Med. 2004;10(7):712-718.

To read the article, access:

Tao, Lijun, Xu, Hongbo and He, Qianggui Potential influences of expression levels of MFGE8 and HMGB1 on the intestinal mucosal barrier function and inflammatory response after blunt abdominal injury in rats. Acta Cirúrgica Brasileira [online], v. 37, n. 3, e370303, 2022.


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