دورية أكاديمية
Elevating EGFR-MAPK program by a nonconventional Cdc42 enhances intestinal epithelial survival and regeneration.
| العنوان: | Elevating EGFR-MAPK program by a nonconventional Cdc42 enhances intestinal epithelial survival and regeneration. |
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| المؤلفون: | Zhang X; Department of Biological Sciences, Division of Life Sciences, School of Arts and Sciences, Rutgers University, Newark, New Jersey, USA., Bandyopadhyay S; Department of Biological Sciences, Division of Life Sciences, School of Arts and Sciences, Rutgers University, Newark, New Jersey, USA., Araujo LP; Department of Microbiology and Immunology, Vagelos College of Physicians and Surgeons, Columbia University, New York, New York, USA., Tong K; Department of Genetics, Division of Life Sciences, School of Arts and Sciences, Rutgers University, New Brunswick, New Jersey, USA., Flores J; Department of Biological Sciences, Division of Life Sciences, School of Arts and Sciences, Rutgers University, Newark, New Jersey, USA., Laubitz D; Department of Pediatrics, University of Arizona, Tucson, Arizona, USA., Zhao Y; Center for Immunity and Inflammation, Rutgers New Jersey Medical School, Newark, New Jersey, USA., Yap G; Center for Immunity and Inflammation, Rutgers New Jersey Medical School, Newark, New Jersey, USA., Wang J; Department of Mechanical and Aerospace Engineering, School of Engineering, Rutgers University, Piscataway, New Jersey, USA., Zou Q; Department of Mechanical and Aerospace Engineering, School of Engineering, Rutgers University, Piscataway, New Jersey, USA., Ferraris R; Department of Pharmacology, Physiology and Neuroscience, Rutgers New Jersey Medical School, Newark, New Jersey, USA., Zhang L; Department of Biological Sciences, Division of Life Sciences, School of Arts and Sciences, Rutgers University, Newark, New Jersey, USA.; Department of Pathology, University Medical Center of Princeton, Plainsboro, New Jersey, USA., Hu W; Rutgers Cancer Institute of New Jersey, New Brunswick, New Jersey, USA., Bonder EM; Department of Biological Sciences, Division of Life Sciences, School of Arts and Sciences, Rutgers University, Newark, New Jersey, USA., Kiela PR; Department of Pediatrics, University of Arizona, Tucson, Arizona, USA., Coffey R; Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, and Epithelial Biology Center, Vanderbilt University Medical Center, Nashville, Tennessee, USA., Verzi MP; Department of Genetics, Division of Life Sciences, School of Arts and Sciences, Rutgers University, New Brunswick, New Jersey, USA., Ivanov II; Department of Microbiology and Immunology, Vagelos College of Physicians and Surgeons, Columbia University, New York, New York, USA., Gao N; Department of Biological Sciences, Division of Life Sciences, School of Arts and Sciences, Rutgers University, Newark, New Jersey, USA.; Rutgers Cancer Institute of New Jersey, New Brunswick, New Jersey, USA. |
| المصدر: | JCI insight [JCI Insight] 2020 Aug 20; Vol. 5 (16). Date of Electronic Publication: 2020 Aug 20. |
| نوع المنشور: | Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S. |
| اللغة: | English |
| بيانات الدورية: | Publisher: American Society for Clinical Investigation Country of Publication: United States NLM ID: 101676073 Publication Model: Electronic Cited Medium: Internet ISSN: 2379-3708 (Electronic) Linking ISSN: 23793708 NLM ISO Abbreviation: JCI Insight Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: Ann Arbor, Michigan : American Society for Clinical Investigation, [2016]- |
| مواضيع طبية MeSH: | ErbB Receptors/*metabolism , Intestinal Mucosa/*physiology , Regeneration/*physiology , cdc42 GTP-Binding Protein/*metabolism, Alternative Splicing ; Animals ; Cell Survival ; Endocytosis/physiology ; HEK293 Cells ; Humans ; Intestinal Mucosa/drug effects ; Intestinal Mucosa/radiation effects ; MAP Kinase Signaling System ; Mice, Knockout ; Mice, Transgenic ; cdc42 GTP-Binding Protein/genetics |
| مستخلص: | The regulatory mechanisms enabling the intestinal epithelium to maintain a high degree of regenerative capacity during mucosal injury remain unclear. Ex vivo survival and clonogenicity of intestinal stem cells (ISCs) strictly required growth response mediated by cell division control 42 (Cdc42) and Cdc42-deficient enteroids to undergo rapid apoptosis. Mechanistically, Cdc42 engaging with EGFR was required for EGF-stimulated, receptor-mediated endocytosis and sufficient to promote MAPK signaling. Proteomics and kinase analysis revealed that a physiologically, but nonconventionally, spliced Cdc42 variant 2 (V2) exhibited stronger MAPK-activating capability. Human CDC42-V2 is transcriptionally elevated in some colon tumor tissues. Accordingly, mice engineered to overexpress Cdc42-V2 in intestinal epithelium showed elevated MAPK signaling, enhanced regeneration, and reduced mucosal damage in response to irradiation. Overproducing Cdc42-V2 specifically in mouse ISCs enhanced intestinal regeneration following injury. Thus, the intrinsic Cdc42-MAPK program is required for intestinal epithelial regeneration, and elevating this signaling cascade is capable of initiating protection from genotoxic injury. |
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| معلومات مُعتمدة: | F31 DK121428 United States DK NIDDK NIH HHS; P30 DK058404 United States DK NIDDK NIH HHS; R21 AI126305 United States AI NIAID NIH HHS; R21 CA178599 United States CA NCI NIH HHS; R21 AI146817 United States AI NIAID NIH HHS; R01 DK102934 United States DK NIDDK NIH HHS; R01 DK119198 United States DK NIDDK NIH HHS; R01 AT010243 United States AT NCCIH NIH HHS; P50 CA236733 United States CA NCI NIH HHS; R01 DK132885 United States DK NIDDK NIH HHS; P30 CA072720 United States CA NCI NIH HHS; R35 CA197570 United States CA NCI NIH HHS; F32 CA235829 United States CA NCI NIH HHS; R01 AI144808 United States AI NIAID NIH HHS; R01 DK098378 United States DK NIDDK NIH HHS; R01 CA190558 United States CA NCI NIH HHS; K99 CA245123 United States CA NCI NIH HHS |
| فهرسة مساهمة: | Keywords: Adult stem cells; Gastroenterology; Mouse models; Stem cells |
| المشرفين على المادة: | 0 (Cdc42 protein, mouse) EC 2.7.10.1 (EGFR protein, mouse) EC 2.7.10.1 (ErbB Receptors) EC 3.6.5.2 (cdc42 GTP-Binding Protein) |
| تواريخ الأحداث: | Date Created: 20200721 Date Completed: 20210611 Latest Revision: 20240329 |
| رمز التحديث: | 20240329 |
| مُعرف محوري في PubMed: | PMC7455142 |
| DOI: | 10.1172/jci.insight.135923 |
| PMID: | 32686657 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 2379-3708 |
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| DOI: | 10.1172/jci.insight.135923 |