ArticleDigestive diseases and sciences2015
Phosphorylation of Smad2/3 at specific linker threonine indicates slow-cycling intestinal stem-like cells before reentry to cell cycle.
Article in Digestive diseases and sciences, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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9 citing papers in PubMed.
- Dietary Iron Alleviates Dextran Sodium Sulfate-Induced Intestinal Injury by Regulating Regeneration of Intestinal Stem Cells in Weaned Mice.Biological trace element research · 2025Article
- A Short-Term Model of Colitis-Associated Colorectal Cancer That Suggests Initial Tumor Development and the Characteristics of Cancer Stem Cells.International journal of molecular sciences · 2023Article
- Docetaxel suppressed cell proliferation through Smad3/HIF-1α-mediated glycolysis in prostate cancer cells.Cell communication and signaling : CCS · 2022Article
- Specific Smad2/3 Linker Phosphorylation Indicates Esophageal Non-neoplastic and Neoplastic Stem-Like Cells and Neoplastic Development.Digestive diseases and sciences · 2021Article
- Long-term model of colitis-associated colorectal cancer suggests tumor spread mechanism and nature of cancer stem cells.Oncology letters · 2021Article
- Article
- MiR-1 suppresses tumor cell proliferation in colorectal cancer by inhibition of Smad3-mediated tumor glycolysis.Cell death & disease · 2017Article
- Association of TGFβ signaling with the maintenance of a quiescent stem cell niche in human oral mucosa.Histochemistry and cell biology · 2016Article
- Reversible Human TGF-β Signal Shifting between Tumor Suppression and Fibro-Carcinogenesis: Implications of Smad Phospho-Isoforms for Hepatic Epithelial-Mesenchymal Transitions.Journal of clinical medicine · 2016Review
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Abstract
backgroundQuiescent (slow-cycling) and active (rapid-cycling) stem cells are demonstrated in small intestines. We have identified significant expression of Smad2/3, phosphorylated at specific linker threonine residues (pSmad2/3L-Thr), in murine stomach, and suggested these cells are epithelial stem cells.
aimHere, we explore whether pSmad2/3L-Thr could serve as a biomarker for small intestine and colon stem cells.
methodsWe examined small intestines and colons from C57BL/6 mice and colons with dextran sulfate sodium (DSS)-induced colitis. We performed double-immunofluorescent staining of pSmad2/3L-Thr with Ki67, cytokeratin 8, chromogranin A, CDK4, DCAMKL1, and Musashi-1. Small intestines and colons from Lgr5-EGFP knock-in mice were examined by pSmad2/3L-Thr immunofluorescent staining. To examine BrdU label retention of pSmad2/3L-Thr immunostaining-positive cells, we collected specimens after BrdU administration and observed double-immunofluorescent staining of pSmad2/3L-Thr with BrdU.
resultsIn small intestines and colons, pSmad2/3L-Thr immunostaining-strongly positive cells were detected around crypt bases. Immunohistochemical co-localization of pSmad2/3L-Thr with Ki67 was not observed. pSmad2/3L-Thr immunostaining-strongly positive cells showed co-localization with cytokeratin 8, CDK4, and Musashi-1 and different localization from chromogranin A and DCAMKL1 immunostaining-positive cells. Under a light microscope, pSmad2/3L-Thr immunostaining-strongly positive cells were morphologically undifferentiated. In Lgr5-EGFP knock-in mice, some but not all pSmad2/3L-Thr immunostaining-strongly positive cells showed co-localization with Lgr5. pSmad2/3L-Thr immunostaining-strongly positive cells showed co-localization with BrdU at 5, 10, and 15 days after administration. In DSS-induced colitis, pSmad2/3L-Thr and Ki67 immunostaining-positive cells increased in the regeneration phase and decreased in the injury phase.
conclusionIn murine small intestines and colons, we suggest pSmad2/3L-Thr immunostaining-strongly positive cells are epithelial stem-like cells just before reentry to the cell cycle.
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