Loss of primary cilia promotes inflammation and carcinogenesis.

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. © 2022 The Authors. Published under the terms of the CC BY NC ND 4.0 license.

Citation

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. Loss of primary cilia promotes inflammation and carcinogenesis. EMBO reports. 2022 Oct 25;23(12):e55687

Mesh Tags

Substances

PMID: 36281991

search → result