Endometriosis Leads to an Increased Trefoil Factor 3 Concentration in the Peritoneal Cavity but Does Not Alter Systemic Levels

Abstract

This study analyzed whether trefoil factor 3 (TFF3) is locally elevated and correlated with common biomarkers and inflammatory processes in endometriosis. Peritoneal fluid (PF) was obtained from 50 women and serum from 124 women with or without endometriosis. Experimental endometriosis was induced in female C57BL/6 mice by syngeneic transplantation of uterine tissue to the abdominal wall. Levels of TFF3 in PF of women with endometriosis were significantly increased ( P < .05) and correlated with local levels of known biomarkers for endometriosis: cancer antigen (CA) 125, CA-19-9, interleukin 8, monocyte chemotactic protein 1, and matrix metalloproteinase 7. Serum levels of TFF3 in women were significantly influenced by the menstrual cycle but were independent from disease state. In mice, local TFF3 levels were significantly elevated in early endometriosis (up to 4 weeks after transplantation, P < .001) and corresponded to increases in spleen weight as marker for systemic inflammation. This study provides the first evidence that TFF3 is locally elevated in the peritoneal cavity in endometriosis and might play a role in disease pathogenesis and its associated inflammatory processes. Furthermore, the results show that TFF3 is regulated through the menstrual cycle. With respect to animal models, syngeneic mouse model does reflect local TFF3 upregulation in the peritoneal cavity affected by endometriosis.

The trefoil factor family 1 (TFF‐1) and 3 (TFF‐3) are upregulated in the saliva, gingival crevicular fluid and serum of periodontitis patients

“…TFF peptides have essential roles in the defense and repair of the tissues through various mechanisms that participate in epithelial restitution, cell migration as well as angiogenesis, antiapoptosis, promoting leukocyte migration, and inflammatory immune processes (Cook et al., 1999; Kjellev, 2009). Pathologic expression of TFF peptides has been shown in a variety of chronic inflammatory diseases (Astor et al., 2011; Henze et al., 2017). Regarding periodontal inflammation, very few studies investigated these peptides in saliva or gingival tissues of patients with peridontal disease (Chaiyarit, Chayasadom, et al., 2012; Hormdee et al., 2019; Meesala et al., 2018).…”

Stool and urine trefoil factor 3 levels: associations with symptoms, intestinal permeability, and microbial diversity in irritable bowel syndrome

“…For example, women with endometriosis also report abdominal pain, constipation, bloating and intestinal gas (Ek et al , 2015). Henze et al (Henze et al , 2016) investigated women with endometriosis and found that peritoneal fluid TFF3 levels were higher in these women when compared to those without endometriosis. Of note, regardless of endometriosis status, the researchers observed menstrual cycle phase differences in serum TFF3 levels (Henze et al , 2016).…”

“…Henze et al (Henze et al , 2016) investigated women with endometriosis and found that peritoneal fluid TFF3 levels were higher in these women when compared to those without endometriosis. Of note, regardless of endometriosis status, the researchers observed menstrual cycle phase differences in serum TFF3 levels (Henze et al , 2016). The difference in the relationship of stool TFF3 and intestinal permeability between those on and off hormone contraception (Table 3) reinforces the importance of considering reproductive status and hormone therapy when testing biomarkers in this predominantly female patient group.…”

“…As noted above, TFF3 can be expressed in other tissues such as endometrium and breast, where TFF3 expression is influenced by estrogen (May and Westley, 2015) and menstrual cycle phase (Henze et al , 2016). However, it is not known whether sex hormones influence urine and/or stool levels of TFF3 in IBS.…”

Trefoil factors — new markers of gastrointestinal mucosal barrier

“…Показано усиление влияние экспрессии трефоиловых факторов на клетки ретинобластомы [24]. Также показано участие TFF в патогенезе заболеваний легких [42,48], гинекологических заболеваний [1,26,36], болезни Альцгеймера [39].…”