Year: 2022
Type: article
Abstract: Primary cilia (PC) are important signaling hubs, and we here explored their role in colonic pathology. In the colon, PC are mostly present on fibroblasts, and exposure of mice to either chemically induced colitis‐associated colon carcinogenesis (CAC) or dextran sodium sulfate (DSS)‐induced acute colitis decreases PC numbers. We generated conditional knockout mice with reduced numbers of PC on colonic fibroblasts. These mice show increased susceptibility to CAC, as well as DSS‐induced colitis. Secretome and immunohistochemical analyses of DSS‐treated mice display an elevated production of the proinflammatory cytokine IL‐6 in PC‐deficient colons. An inflammatory environment diminishes PC presence in primary fibroblast cultures, which is triggered by IL‐6 as identified by RNA‐seq analysis together with blocking experiments. These findings suggest an activation loop between IL‐6 production and PC loss. An analysis of PC presence on biopsies of patients with ulcerative colitis or colorectal cancer (CRC) reveals decreased numbers of PC on colonic fibroblasts in pathological compared with surrounding normal tissue. Taken together, we provide evidence that a decrease in colonic PC numbers promotes colitis and CRC. Primary cilia are present on colonic fibroblasts and their decrease in number promotes colitis and colon carcinogenesis. In colitis, primary cilia loss appears to be ultimately linked to IL‐6 signaling. Primary cilia are present on colonic fibroblasts and their decrease in number promotes colitis and colon carcinogenesis. In colitis, primary cilia loss appears to be ultimately linked to IL‐6 signaling.
Source: EMBO Reports
Authors: Conception Paul, Ruizhi Tang, Ciro Longobardi, Rossano Lattanzio, Thibaut Eguether, Hulya Turali, Julie Bremond, Chloé Maurizy, Monica Gabola, Sophie Poupeau, Andrei Turtoi, Emilie Denicolai, Maria Concetta Cufaro, Magali Svrcek, Philippe Seksik, Vincent Castronovo, Philippe Delvenne, Vincenzo de Laurenzi, Quentin Da Costa, François Bertucci, Bénédicte Lemmers, Damiana Pieragostino, Emilie Mamessier, Carsten Janke, Valérie Pinet, Michael Hahne
Institutions: Centre National de la Recherche Scientifique, Institut de Génétique Moléculaire de Montpellier, Amsterdam UMC Location University of Amsterdam, Amsterdam University Medical Centers, Cancer Center Amsterdam, University of Amsterdam, University of Chieti-Pescara, Inserm, Sorbonne Université, Centre de Recherche Saint-Antoine, Institut de Recherche en Cancérologie de Montpellier, Centre de Recherche en Cancérologie de Marseille, Assistance Publique – Hôpitaux de Paris, Hôpital Saint-Antoine, University of Liège, Centre Hospitalier Universitaire de Liège, Université Paris-Sud, Université Paris Sciences et Lettres, Université Paris-Saclay, Intégrité du génome, ARN et cancer, Institut Curie
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $6,100
OpenAlex ID: W4307201626