Infiltrating CCR2+ monocytes and their progenies, fibrocytes, contribute to colon fibrosis by inhibiting collagen degradation through the production of TIMP-1

Abstract

Intestinal fibrosis is a serious complication in inflammatory bowel disease (IBD). Despite the remarkable success of recent anti-inflammatory therapies for IBD, incidence of intestinal fibrosis and need for bowel resection have not significantly changed. To clarify the contribution of haematopoietic-derived cells in intestinal fibrosis, we prepared bone marrow (BM) chimeric mice (chimeras), which were reconstituted with BM cells derived from enhanced green fluorescent protein (EGFP)-transgenic mice or CC chemokine receptor 2 (CCR2)-deficient mice. After 2 months of transplantation, BM chimeras were treated with azoxymethane/dextran sodium sulphate. During chronic inflammation, CCR2 + BM-derived monocyte and fibrocyte infiltration into the colon and CC chemokine ligand 2 production increased, leading to colon fibrosis in EGFP BM chimeras. In CCR2-deficient BM chimeras, monocyte and fibrocyte numbers in the colonic lamina propria significantly decreased, and colon fibrosis was attenuated. In colon tissue, mRNA expression of tissue inhibitor of metalloproteinase (TIMP)-1 but not of collagen I, transforming growth factor-β1 or matrix metalloproteinases was significantly different between the two chimeras. CCR2 + monocytes and fibrocytes showed high Timp1 mRNA expression. Our results suggest that infiltrating CCR2 + monocytes and their progenies, fibrocytes, promote colon fibrosis by inhibiting collagen degradation through TIMP-1 production.

Fibrocytes, Wound Healing, and Corneal Fibrosis

“…42 Driven by TGF-β 1 , the fibrocytes may differentiate into myofibroblasts, which are recognized as the effector cells of fibrogenesis. 11,12,15,[77][78][79] Finally, Kuroda et al 80 suggest that fibrocytes promote colon fibrosis by inhibiting collagen degradation through the production of TIMP-1.…”

Restraint Stress in Hypertensive Rats Activates the Intestinal Macrophages and Reduces Intestinal Barrier Accompanied by Intestinal Flora Dysbiosis

“…Therefore, the regulation of the cells is essential for reducing colon fibrosis in patients with inflammatory bowel disease (IBD). [54][55][56] The effect of restraint stress treatment on changes in colonic fibrosis was examined by Sirud Red staining and Masson's trichrome staining with the observation method of light microscope, polarization microscope and TEM, it is found that there is a clear correlation between increased interstitial collagen and increased plasma concentration of TIMP-1 with morphological and biochemical evidence of ECM accumulation. All these indicate that dysregulated matrix remodeling may be one of the reasons for inhibiting stress and HTN-induced intestinal fibrosis pathology.…”

Role of circulating fibrocytes in the diagnosis of acute appendicitis

“…This study demonstrates not only that CFP is increased in patients with acute appendicitis, but that the proportion of fibrocytes in circulating white cells may be of diagnostic value in patients presenting with suspected appendicitis. The CFP increases in response to systemic and localized inflammatory conditions 32,[40][41][42] . Circulating fibrocytes contribute to the intestinal mesenchymal cells, which comprise a spectrum of cell types that are similar in origin, function and molecular markers.…”