metanephric mesenchyme-derived foxd1+ mesangial precursor cells alleviate mesangial proliferative glomerulonephritis

Mesangial proliferative glomerulonephritis (mspgn) is a glomerular disease characterized by the proliferation of mesangial cells and the accumulation of mesangial matrix. no effective treatment is currently able to stop or reverse the disease process. here, we isolated metanephric mesenchyme-derived foxd1+ mesangial precursor cells from e13.5 foxd1cre; dtrflox double transgenic embryo mice. the foxd1+ cells showed the cell-specific expression of high levels of foxd1 without six2 and manifested specific cell surface markers of mesenchymal stem cells while retaining their differentiation potential. next, an anti-thy1 mspgn rat model was established, and the foxd1+ cells were injected into the tail veins 24 h later. we found that the foxd1+ cells could improve the pathological changes to the kidney and significantly reduce proteinuria by inhibiting the sonic hedgehog pathway. moreover, the foxd1+ cells could inhibit pdgf-bb-induced activation of mesangial cells by secreting multiple cytokines, including hepatocyte growth factor. our study uncovered the novel function of foxd1+ mesangial precursor cells in repairing the damaged mesangium, stabilizing the structure and function of mesangial cells, and restoring their therapeutic effect on the mspgn.