Expression of A-kinase anchor protein 13 and Rho-associated coiled-coil containing protein kinase in restituted and regenerated mucosal epithelial cells following mucosal injury and colorectal cancer cells in mouse models

Kangawa, Yumi; Yoshida, Toshinori; Tanaka, Takeshi; Kataoka, Akira; Koyama, Naomi; Ohsumi, Tomoka; Hayashi, Shim-mo; Shibutani, Makoto

doi:10.1016/j.etp.2017.04.002

Cited by 3 publications

(4 citation statements)

References 39 publications

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“…Initial mucosal damage may be immediately rescued by restitution, which is the migration of monolayered epithelial cells from the surrounding mucosa reserved at the ulcer edge to cover the denuded area 10 . We and other researchers reported a monolayer of restituted epithelium covering the surface of ulcer areas during the recovery period after DSS administration in mice [11][12][13][14] . Together with the observation of restitution, we reported that small cell clumps remained under the lamina propria after induction of ulcers in DSS-treated mice 11,12 .…”

Section: Introductionmentioning

confidence: 53%

“…Each mouse was evaluated daily for diarrhea, fecal blood (Uropaper® III Eiken, Eiken Chemical Co., Inc., Tokyo, Japan), and body weight loss for the sake of being used as the disease activity index (DAI), as previously described 11,23 (Supplemental Table 1). Fecal blood was scored by cutting the collected feces in half, putting them in a PCR tube containing physiological saline for 30 seconds, and subsequently dipping a Uropaper ® III Eiken in the tube for another 1 minute.…”

Section: Assessment Of Disease Activity Index Of Colitismentioning

confidence: 99%

“…Histological evaluation was performed by scoring the extent of tissue injury based on in ammation, mucosal loss, and edema using H&E-stained specimens, as previously described 12 (Supplemental Table 2). Epithelial clumps at the lamina propria were observed as previously reported 11 and classi ed into seven types based on morphological characteristics. The clumps were subclassi ed into type 1 to 4, according to the number of nuclei: type 1 exhibited a single nucleus; type 2, two or three nuclei; type 3, four to nine nuclei; and type 4, 10 nuclei or more (Supplemental Fig.…”

Section: Tissue Preparation and Histological Evaluation Of Colitismentioning

confidence: 99%

“…The epithelial clumps appeared alongside or before the period of restitution. These clumps consisted of a few epithelial cells; immunohistochemical studies demonstrated that they expressed cytokeratin AE1/AE3 and lacked the mesenchymal marker vimentin; cell proliferation markers proliferating cell nuclear antigen (PCNA) and 5bromo-2'-deoxyuridine (BrdU); and mucin, as indicated by PAS reaction 11 . However, the origin of the epithelial clumps is unknown.…”

Section: Introductionmentioning

confidence: 99%

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Characteristics of Colon Crypt Stem Cells in Preserved Epithelial Cell Clumps in Dextran Sulfate Sodium-induced Mouse Model of Ulcerative Colitis

Kobayashi

Yamashita

Ichikawa

et al. 2021

Preprint

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Crypt stem cells rescue the colorectum from refractory ulcers in ulcerative colitis (UC). We previously reported that clumps of a few epithelial cells were scattered in ulcer regions in a dextran sulfate sodium (DSS)-induced mouse model of UC; however, the origin of the clumps is unknown. We determined the immunohistochemical expression of stem-cell markers in the epithelial clumps in female Balb/c mice administered DSS in drinking water for 6 days, followed by withdrawal of DSS for 6 days. Similar to the characteristics of UC, the ulcers were more severe in the distal region close to the anus than in the proximal region of the colorectum. Quantitative analyses revealed that the epithelial clumps appeared in relation to the severity of ulcer, and they expressed the cell adhesion molecules E-cadherin and β-catenin. Among stem cell markers, the epithelial clumps primarily expressed + 5 cell marker Dll1, followed by + 4 cell marker Bmi1 and crypt stem cell marker Lgr5 in that order. Nuclear expression of Sox9, but not Ki-67 and β-catenin was identified in the clumps. The present results suggest that the epithelial clumps comprised crypt-derived stem cells with the potential to regenerate crypts, which could serve as a potential treatment strategy for UC.

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Section: Introductionmentioning

confidence: 53%

Section: Assessment Of Disease Activity Index Of Colitismentioning

confidence: 99%

Section: Tissue Preparation and Histological Evaluation Of Colitismentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Characteristics of Colon Crypt Stem Cells in Preserved Epithelial Cell Clumps in Dextran Sulfate Sodium-induced Mouse Model of Ulcerative Colitis

Kobayashi

Yamashita

Ichikawa

et al. 2021

Preprint

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Ectopically Localized Epithelial Cell Clumps in Ulcers Are Derived from Reserved Crypt Stem Cells in a Mouse Model of Ulcerative Colitis

et al. 2022

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Anorectal Remodeling in the Transitional Zone with Increased Expression of LGR5, SOX9, SOX2, and Keratin 13 and 5 in a Dextran Sodium Sulfate-Induced Mouse Model of Ulcerative Colitis

Kobayashi,

Usui,

Elbadawy

et al. 2024

IJMS

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Although hyperplasia of the anorectal transitional zone (TZ) has been reported in mouse models of ulcerative colitis, the mechanisms underlying this phenomenon are not fully understood. We characterized keratin subtypes and examined the expression of stem cell markers in the TZ. Dextran sodium sulfate-treated mice showed abnormal repair of the anorectal region, which consisted of mixed hyperplastic TZ and regenerating crypts. Liquid chromatography-tandem mass spectrometry from the paraffin-embedded TZ in the treated mice revealed that the major keratins were type I cytokeratin (CK)13 and type II CK5, but notable expression of type I CK10 and CK42 and type II CK1, CK4, CK6a, CK8, and CK15 was also detected. Hyperplastic TZ was characterized by the expression of tumor protein 63, sex-determining region Y-box 2 (SOX2), SOX9, and leucine-rich repeat-containing G-protein coupled receptor 5 (Lgr5). Lgr5 was highly expressed in the TZ in the early stages of colitis, followed by higher expression levels of SOX2. The TZ-derived organoids expressed LGR5, SOX2, and SOX9. The present study suggests that transitional zones showing abnormal keratin assembly and stem cell activation may interfere with rectal crypt regeneration, leading to pathological anorectal remodeling in severe colitis.

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Expression of A-kinase anchor protein 13 and Rho-associated coiled-coil containing protein kinase in restituted and regenerated mucosal epithelial cells following mucosal injury and colorectal cancer cells in mouse models

Cited by 3 publications

References 39 publications

Characteristics of Colon Crypt Stem Cells in Preserved Epithelial Cell Clumps in Dextran Sulfate Sodium-induced Mouse Model of Ulcerative Colitis

Characteristics of Colon Crypt Stem Cells in Preserved Epithelial Cell Clumps in Dextran Sulfate Sodium-induced Mouse Model of Ulcerative Colitis

Ectopically Localized Epithelial Cell Clumps in Ulcers Are Derived from Reserved Crypt Stem Cells in a Mouse Model of Ulcerative Colitis

Anorectal Remodeling in the Transitional Zone with Increased Expression of LGR5, SOX9, SOX2, and Keratin 13 and 5 in a Dextran Sodium Sulfate-Induced Mouse Model of Ulcerative Colitis

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