Abstract
Obesity-related glomerulopathy (ORG) is described as obesity-driven glomerular hypertrophy. SHP-1 is associated with glomerular pathology. This study is designed to investigate the molecular mechanism of Src homology region 2 domain-containing protein tyrosine phosphatase 1 (SHP-1) in ORG and palmitic acid (PA)-induced podocyte injury. After analysis of clinical samples, an ORG mouse model was established via high-fat diet feeding, followed by detection of physiological and biochemical indexes, glomerular area, and inflammatory factor levels. In vitro cell model was established using (PA). Cell viability, apoptosis, and lipid deposition were determined. SHP-1, nuclear factor-erythroid 2-related factor 2 (Nrf2), phosphatidylinositol 3-kinase (PI3K), and sirtuin 1 (SIRT1) expressions were measured, and their binding relationships were testified. SHP-1 was highly expressed in ORG patients and was associated with renal function indexes. Silencing SHP-1 alleviated symptoms of ORG mice and PA-induced podocyte injury in vitro. SHP-1 bound to PI3K to inhibit PI3K phosphorylation and Nrf2 expression. Nrf2 bound to the SIRT1 promoter to promote SIRT1 transcription. Inhibition of Nrf2 or SIRT1 reversed the role of silencing SHP-1 in podocyte injury. Overall, SHP-1 was highly expressed in ORG and inhibited PI3K phosphorylation to block activation of Nrf2/SIRT1, thereby aggravating ORG-induced renal injury in vivo and PA-induced podocyte injury in vitro.
Published Version
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