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- Title
Bone marrow-derived cells contribute to cerulein-induced pancreatic fibrosis in the mouse.
- Authors
Lin, Wey-Ran; Inatomi, Osamu; Lee, Chung Y.; Kallis, Yiannis N.; Otto, William R.; Jeffery, Rosemary; Poulsom, Richard; Alison, Malcolm R.
- Abstract
Summary Bone marrow (BM) cells may transdifferentiate into circulating fibrocytes and myofibroblasts in organ fibrosis. In this study, we investigated the contribution and functional roles of BM-derived cells in murine cerulein-induced pancreatic fibrosis. C57/BL6 female mice wild-type (WT) or Col 1α1r/r male BM transplant, received supraphysiological doses of cerulein to induce pancreatic fibrosis. The CD45+Col 1+ fibrocytes isolated from peripheral blood (PB) and pancreatic tissue were examined by in situ hybridization for Y chromosome detection. The number of BM-derived myofibroblasts, the degree of Sirius red staining and the levels of Col 1α1 mRNA were quantified. The Y chromosome was detected in the nuclei of PB CD45+Col 1+ fibrocytes, confirming that circulating fibrocytes can be derived from BM. Co-expression of α-smooth muscle actin illustrated that fibrocytes can differentiate into myofibroblasts. The number of BM-derived myofibroblasts, degree of collagen deposition and pro-collagen I mRNA expression were higher in the mice that received Col 1α1r/r BM, (cells that produce mutated, collagenase-resistant collagen) compared to WT BM, indicating that the genotype of BM cells can alter the degree of pancreatic fibrosis. Our data indicate that CD45+Col 1+ fibrocytes in the PB can be BM-derived, functionally contributing to cerulein-induced pancreatic fibrosis in mice by differentiating into myofibroblasts.
- Subjects
BONE marrow; MYOFIBROBLASTS; FIBROBLASTS; IMMUNE system; MESSENGER RNA
- Publication
International Journal of Experimental Pathology, 2012, Vol 93, Issue 2, p130
- ISSN
0959-9673
- Publication type
Article
- DOI
10.1111/j.1365-2613.2011.00804.x