Oestrogen inhibits PTPRO to prevent the apoptosis of renal podocytes

Ren,Wei; Yi,Huiru; Bao,Ying; Liu,Yingru; Gao,Xinru

doi:10.3892/etm.2019.7167

Oestrogen inhibits PTPRO to prevent the apoptosis of renal podocytes

Authors:
- Wei Ren
- Huiru Yi
- Ying Bao
- Yingru Liu
- Xinru Gao
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Affiliations: Department of Internal Medicine, Xi'an Children's Hospital, Xi'an, Shaanxi 710003, P.R. China, Department of Nephrology, Xi'an Children's Hospital, Xi'an, Shaanxi 710003, P.R. China, Department of Medical Ultrasound Center, The Northwest Women's and Children's Hospital, Xi'an, Shaanxi 710061, P.R. China
Published online on: January 14, 2019 https://doi.org/10.3892/etm.2019.7167
Pages: 2373-2380

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Abstract

Podocytes are a major component of the glomerular filtration membrane, and their apoptosis is involved in a variety of nephrotic syndromes. In the current study, the effects and molecular mechanisms of oestrogen on the proliferation and apoptosis of podocytes were investigated to elucidate the role of oestrogen in the pathogenesis of childhood nephrotic syndrome. The cell proliferation of mouse renal podocytes (MPC‑5) and human primary renal podocytes was promoted by 17β‑oestradiol (E2) in what appear to be a time‑dependent manner. Apoptosis was inhibited by E2 and promoted by the E2 antagonist, tamoxifen. The expression of protein tyrosine phosphatase receptor type O (PTPRO) decreased with the increasing dosage of E2, but increased with the increasing dosage tamoxifen in MPC‑5 and human podocytes. The protein, oestrogen receptor (ER)α, was not expressed in MPC‑5 and human podocytes. E2 binding to ERβ completely eliminated PTPRO expression in MPC‑5. In podocytes, PTPRO was phosphorylated by E2 at the Y1007 and associated with tyrosine‑protein kinase JAK2 (JAK2) activation, rather than JAK1 activation. PTPRO was involved in the binding of E2 to signal transducer and activator of transcription (STAT)3 at the Y705 and S727 sites, resulting in the phosphorylation of STAT3 in podocytes. Through PTPRO, E2 also regulated the proliferation and apoptosis of podocytes. In conclusion, oestrogen binding to ERβ, rather than ERα, promoted the proliferation of podocytes and inhibited the apoptosis of podocytes by inhibiting the expression of PTPRO. The mechanism may be associated with the activation of the JAK2/STAT3 signalling pathway. The current study may provide a novel direction for the treatment of childhood nephrotic syndrome.

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