Enterotoxigenic Bacteroides fragilis (ETBF) is an intestinal bacterium that secretes the metalloprotease Bacteroides fragilis toxin (BFT), which induces E-cadherin cleavage and interleukin-8 secretion in human intestinal epithelial cell lines. ETBF-induced E-cadherin cleavage is proposed to be the underlying reason for the promotion of colitis in ETBF-infected mice. However, a BFT-responsive murine cell line has not yet been reported. In the current study, we report that the mouse colonic epithelial cell line CMT93 undergoes E-cadherin ectodomain cleavage, cell rounding, and proliferation in response to BFT treatment. The amino acid sequence of the putative cleavage site of E-cadherin is identical in both BFT-responsive (CMT93) and BFT-nonresponsive (MSIE, CT26, YAMC, and B16) cell lines, suggesting that the E-cadherin amino acid sequence is not responsible for this observation. After E-cadherin ectodomain cleavage, the membrane-bound intracellular E-cadherin domain underwent cleavage by γ-secretase and was subsequently degraded by the proteasome. Moreover, BFT induced the secretion of two chemokines (LIX and KC) and the formation of soluble TNFR1 in the CMT93 cell line. The identification of a BFT-responsive murine cell line may be used to elucidate the mechanism of ETBF pathogenesis in ETBF murine infection models.

Pressure ulcers (PUs) are localized injuries caused by prolonged mechanical loading and ischemia, often leading to delayed healing and high recurrence rates. Although conventional treatments aim to support tissue repair, their efficacy remains limited, prompting interest in noninvasive therapies such as the pulsed electromagnetic field (PEMF). The PEMF has been reported to enhance cellular proliferation, re-epithelialization, and collagen remodeling, but its effects in pressure ulcer models, particularly concerning genetic background, remain unclear. This study investigated the therapeutic effects of the PEMF in a murine pressure ulcer model established by ischemia and reperfusion injury induced with externally attached magnets in two mouse strains, BALB/c and C57BL/6. The PEMF (10 Hz, 24 h per day) was used to treat PU-induced mice from day 4 to day 15 in BALB/c mice and to day 14 in C57BL/6 mice. Wound healing was assessed by gross morphological observation, histological analysis, and digital quantification of epidermal lesion length and collagen-positive area. In BALB/c mice, PEMF-treated wounds showed a modest trend toward improved re-epithelialization and collagen deposition, although the differences were not statistically significant. In contrast, C57BL/6 mice exhibited a significantly shorter length of epidermal lesion in the PEMF group on day 14, indicating enhanced epidermal regeneration. Collagen analysis showed comparable levels between treated and control groups in both strains, with no significant differences observed. To further assess the cellular response to PEMF, a scratch wound assay was conducted using HaCaT cells. Quantitative analysis demonstrated that PEMF treatment accelerated cell migration and wound closure in vitro. These findings suggest that PEMF enhances epidermal regeneration and keratinocyte mobility, with therapeutic responses potentially influenced by genetic background. This study supports the potential application of PEMF in pressure ulcer treatment and underscores the importance of strain selection in preclinical wound healing research.

Enterotoxigenic Bacteroides fragilis (ETBF) secretes Bacteroides fragilis toxin (BFT), a metalloprotease that disrupts intestinal epithelial integrity and activates pro-inflammatory signaling. Although E-cadherin cleavage is a well-established response to BFT, the involvement of other membrane receptors in BFT-induced signaling remains poorly defined. In this study, we examined whether HER2 undergoes proteolytic processing following BFT exposure and whether HER2 contributes to BFT-induced ERK activation. In HT29/c1 and MCF-7 epithelial cells, BFT induced the loss of full-length 185 kDa HER2 and the generation of a membrane-tethered ~95 kDa fragment. This truncated HER2 underwent γ-secretase-dependent intramembrane processing and subsequent proteasomal degradation. Knockdown of MMP-7 or ADAM10 did not prevent HER2 cleavage, indicating that neither protease is required for this process. In addition, BFT-induced ERK phosphorylation was observed in HER2-expressing cells but was abolished in HER2-deficient HT29/c1 clones, whereas E-cadherin cleavage and IL-8 secretion remained detectable. These findings identify HER2 as a previously unrecognized target of BFT-induced proteolytic remodeling and support a contribution of HER2 to BFT-induced ERK activation.