Interleukin-34 Stimulates Gut Fibroblasts to Produce Collagen Synthesis
| Autor: | Alfredo Colantoni, Giuseppe S. Sica, Angela Ortenzi, Federica Laudisi, Sara Di Carlo, Giovanni Monteleone, Davide Di Fusco, Eleonora Franzè, Vincenzo Dinallo, Antonio Di Grazia, Paolo Giuffrida, Antonio Di Sabatino |
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| Rok vydání: | 2020 |
| Předmět: |
Stromal cell
MAP Kinase Signaling System medicine.medical_treatment p38 mitogen-activated protein kinases Receptor Macrophage Colony-Stimulating Factor Constriction Pathologic Crohn Disease medicine Humans Intestinal Mucosa Receptor Cells Cultured Wound Healing Gene knockdown business.industry Interleukins Gastroenterology General Medicine Fibroblasts Fibrosis Immunohistochemistry Molecular biology Intestines Blot Cytokine Interleukin 34 Collagen Wound healing business |
| Zdroj: | Journal of Crohn's and Colitis. 14:1436-1445 |
| ISSN: | 1876-4479 1873-9946 |
| Popis: | Background and AimThe mechanisms underlying the formation of intestinal fibrostrictures [FS] in Crohn’s disease [CD] are not fully understood, but activation of fibroblasts and excessive collagen deposition are supposed to contribute to the development of FS. Here we investigated whether interleukin-34 [IL-34], a cytokine that is over-produced in CD, regulates collagen production by gut fibroblastsMethodsIL-34 and its receptor macrophage colony-stimulating factor receptor 1 [M-CSFR-1] were evaluated in inflammatory [I], FS CD, and control [CTR] ileal mucosal samples by real-time polymerase chain reaction [RT-PCR], western blotting, and immunohistochemistry. IL-34 and M-CSFR-1 expression was evaluated in normal and FS CD fibroblasts. Control fibroblasts were stimulated with IL-34 in the presence or absence of a MAP kinase p38 inhibitor, and FS CD fibroblasts were cultured with a specific IL-34 antisense oligonucleotide, and collagen production was evaluated by RT-PCR, western blotting, and Sircol assay. The effect of IL-34 on the wound healing capacity of fibroblasts was evaluated by scratch test.ResultsWe showed enhanced M-CSFR-1 and IL-34 RNA and protein expression in FS CD mucosal samples as compared with ICD and CTR samples. Immunohistochemical analysis showed that stromal cells were positive for M-CSFR-1 and IL-34. Enhanced M-CSFR-1 and IL-34 RNA and protein expression was seen in FS CD fibroblasts as compared with CTR. Stimulation of control fibroblasts with IL-34 enhanced COL1A1 and COL3A1 expression and secretion of collagen through a p38 MAP kinase-dependent mechanism, and wound healing. IL-34 knockdown in FS CD fibroblasts was associated with reduced collagen production and wound repair.ConclusionsData indicate a prominent role of IL-34 in the control of intestinal fibrogenesis. |
| Databáze: | OpenAIRE |
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