The effect of transforming growth factor β(1) in the transition of bone marrow-derived macrophages into myofibroblasts during renal fibrosis

Abstract

To study which subgroup of bone marrow derived cells formed myofibroblasts and the mechanism that transforming growth factor β(1)(TGFβ(1)) regulates the formation of bone marrow derived macrophages into myofibroblasts during renal fibrosis. Chimeric mice were generated by lethally irradiation of C57 mice followed by transfusion of green fluorescent protein (GFP) labeled bone marrow cells. Complete marrow reconstitution was developed until 12 weeks after transplantation. The mice were randomly divided into Sham operation group, unilateral ureteral obstruction (UUO) 3 days group, UUO5 days group, UUO7 days group and UUO7 with TGFβ(1) treatment group. Each group had four mice. Flow cytometry was used to evaluate cell components. Compared with Sham operation group the proportions of GFP(+) CD(14)(+)α-smooth muscle actin(α-SMA)(+) cells, GFP+ CD(44)(+)CD(105)(+)α-SMA(+) cells and GFP(+) F4/80(+) α-SMA(+) cells in each UUO group were progressively increased and the transformation rate in UUO7 day group was the highest. The GFP(+) F4/80(+) α-SMA(+) cells accounted for the largest population. TGFβ(1) promoted the transformation of bone marrow derived macrophages into myofibroblasts. Compared with Sham operation group or UUO7 day group, the proportion of GFP(+) F4/80(+) α-SMA(+) cells increased in UUO7 day TGFβ(1) treatment group. Compared with Sham operation group (or UUO7 days group) the protein expressions of F4/80, α-SMA, Collagen Ⅰ increased in UUO7 with TGFβ(1) group. Bone marrow derived macrophages are considered as the main type of myofibroblast precursors during the development of renal fibrosis. TGFβ(1) regulates the transformation of bone marrow-derived macrophages into myofibroblasts. This process contributes to progressive renal fibrosis and deterioration of renal function.