title: Bone marrow-derived cells contribute to cerulein-induced pancreatic fibrosis in the mouse.
abstract: 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 1α1(r/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 1α1(r/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.
authors.affiliation: Centre for Diabetes, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK.
authors.forename: Wey-Ran
authors.initials: WR
authors.lastname: Lin
authors.forename: Osamu
authors.initials: O
authors.lastname: Inatomi
authors.forename: Chung Y
authors.initials: CY
authors.lastname: Lee
authors.forename: Yiannis N
authors.initials: YN
authors.lastname: Kallis
authors.forename: William R
authors.initials: WR
authors.lastname: Otto
authors.forename: Rosemary
authors.initials: R
authors.lastname: Jeffery
authors.forename: Richard
authors.initials: R
authors.lastname: Poulsom
authors.forename: Malcolm R
authors.initials: MR
authors.lastname: Alison
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D016026:Bone Marrow Transplantation; D002465:Cell Movement / Q000187:drug effects; D054338:Cell Transdifferentiation / Q000187:drug effects; D002108:Ceruletide / Q000633:toxicity*; D003094:Collagen / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D005355:Fibrosis; D017493:Leukocyte Common Antigens / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010182:Pancreatic Diseases / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology*
chemical_list: D002108:Ceruletide; D003094:Collagen; D017493:Leukocyte Common Antigens; C516770:Ptprc protein, mouse