Renalase, a recently discovered secreted
flavoprotein, exerts anti-apoptotic and anti-inflammatory effects against renal injury in acute and chronic animal models. However, whether
Renalase elicits similar effects in the development of
diabetic nephropathy (DN) remains unclear. The studies presented here tested the hypothesis that
Renalase may play a key role in the development of DN and may have therapeutic potential for DN.
Renalase expression was measured in human kidney biopsies with DN and in kidneys of db/db mice. The role of
Renalase in the development of DN was examined using a genetically engineered mouse model:
Renalase knockout mice with db/db background. The renoprotective effects of
Renalase in DN was evaluated in db/db mice with
Renalase overexpression. In addition, the effects of
Renalase on high
glucose-induced mesangial cells were investigated.
Renalase was down-regulated in human diabetic kidneys and in kidneys of db/db mice compared with healthy controls or db/m mice.
Renalase homozygous knockout increased arterial blood pressure significantly in db/db mice while heterozygous knockout did not.
Renalase heterozygous knockout resulted in elevated
albuminuria and increased renal mesangial expansion in db/db mice. Mesangial
hypertrophy, renal
inflammation, and pathological injury in diabetic
Renalase heterozygous knockout mice were significantly exacerbated compared with wild-type littermates. Moreover,
Renalase overexpression significantly ameliorated renal injury in db/db mice. Mechanistically,
Renalase attenuated high
glucose-induced profibrotic gene expression and p21 expression through inhibiting extracellular regulated
protein kinases (ERK1/2). The present study suggested that
Renalase protected against the progression of DN and might be a novel therapeutic target for the treatment of DN.