Article révisé par les pairs
Résumé : Aristolochic acid nephropathy (AAN) characterized by rapidly progressing renal fibrosis of toxic origin is primed by acute injury of proximal tubular epithelial cells (PTEC). Antitransforming growth factor β (TGFβ) antibody has been shown to improve renal fibrosis invarious models of glomerular diseases, but its roles in primary tubulo-interstitial nephropathies are not yet well known. We studied the efficacy of a murine pan-specific anti-TGFβ monoclonal antibody (1D11) in an acute phase of AAN. Weight matched rats were daily sc. injected with AA (15 mg/kg/day) or vehicle (polyethylene glycol-PEG) from day 0 to day 5. Four groups (n=6/group) were randomly assessed: PEG+1D11; AA alone; AA+1D11 and AA+control isotype (13C4). The 1D11 and 13C4 antibodies (5 mg/kg) were administered ip. at days -1, 0, 2 and 4. After 5 days of treatment, renal function and morphology remained normal in the control group PEG+1D11. 1D11 statistically attenuated AA induced acute kidney injury, as attested by less increased creatininemia and urinary excretion of N-acetyl-β-glucosaminidase, less severe necrosis of PTEC from S3 segment and reduced macrophages infiltration in outer medulla. Intrarenal regulatory T cells infiltration and neo-angiogenesis around the injured areas were also reduced by 1D11. The proliferation of PTEC from S1-3 segments was maintained with 1D11. Our results demonstrate that anti-TGFβ antibody significantly attenuates acute PTEC injury, reduces macrophages infiltration and modulates the regulatory T cells immune response. Therefore, 1D11 could be a potential, new renoprotective therapy interfering with early fibrogenesis events after a toxic insult.

Documents en relation

DI-fusion