Mitotic spindle positioning protein (MISP) deficiency exacerbates dextran sulfate sodium (DSS)-induced colitis in mice

Abstract

Inflammatory bowel disease (IBD) is classified into two types: Crohn's disease and ulcerative colitis. In IBD, the imbalance between the pro-inflammatory and anti-inflammatory cytokines prevents recovery from the inflammatory state, resulting in chronic inflammation in the colon.The mitotic spindle positioning protein (MISP) is localized to the apical membrane in the colon.In this study, we observed increased expression of MISP in the intestinal epithelial cells in dextran sulfate sodium (DSS)-induced colitis in mice. MISP-deficient mice receiving DSS showed significant exacerbation of colitis (e.g., weight loss, loss of the crypts). The intestinal epithelial cells of the MISP-deficient mice showed a trend towards decreased cell proliferation after DSS treatment. Reverse transcription followed by quantitative polymerase chain reaction revealed that the expression levels of Tgfb1, an anti-inflammatory cytokine, were significantly reduced in the colon of MISP-deficient mice compared with the wild-type mice regardless of DSS treatment.These findings indicate that MISP may play a role in the recovery of the colon after inflammation through its anti-inflammatory and proliferative activities, suggesting that MISP may be a new therapeutic target for IBD.

Mitotic Spindle Positioning (MISP) Facilitates Colorectal Cancer Progression by Forming a Complex with Opa Interacting Protein 5 (OIP5) and Activating the JAK2-STAT3 Signaling Pathway

“…We evaluated weight changes, Disease Activity Index (DAI) scores, and survival rates in the AOM/DSS mouse model to examine the role of MISP in chronic inflammation. The DAI score was determined by combining three individual scores: the rate of weight loss, stool characteristics, and the severity of hematochezia, to assess the severity of colitis [ 18 , 23 , 24 ]. Our observations revealed no significant differences in the rates of weight change, DAI scores, or survival rates between Misp KO mice and their wild-type (WT) counterparts ( Figure 3 ).…”

“…It is important to note that intestinal diseases can be categorized as either acute, typically lasting a few weeks (usually between 7 to 14 days), or chronic, persisting for several months or longer [ 31 ]. These findings suggest that MISP may offer protection against acute inflammation in the colon [ 18 ] but does not appear to have the same effect on chronic inflammation. Subsequently, we assessed tumor development in the colons of Misp KO mice using a colitis-induced colorectal tumor model.…”

“…It is conceivable that another contributing factor could be a decrease in the expression of TGF-β1. Previously, we have found that Misp KO mice exhibit decreased TGF-β1 expression in their colonic mucosa [ 18 ]. TGF-β1 is recognized for its dual role, acting both as a tumor suppressor in moderately to highly differentiated primary tumors and as a tumor growth factor in metastatic CRC cells [ 44 ].…”

“…Misp KO mice, which were developed in the C57BL/6J strain, were generated as previously described [ 18 ]. The animal facilities were climate-controlled, maintaining an ambient temperature of 22 ± 2 °C and a relative humidity of 40–60%.…”

“…Misp KO mice were healthy and showed no histological abnormalities in any of their organs, including the intestine. However, Misp KO mice have been found to exhibit significant exacerbation of colitis symptoms, such as weight loss and loss of crypt tissue, in DSS-induced colitis, suggesting that MISP plays a protective role against colitis [ 18 ]. MISP is a substrate of Polo-like kinase 1 (PLK1) and is phosphorylated by PLK1 to form a complex with the +TIP-binding protein p150 glued , which is a subunit of the dynein–dynactin complex.…”