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(Pro)renin receptor is involved in mesangial fibrosis and matrix expansion

Kaori Narumi1, Emiko Sato2,3, Takuo Hirose2

  • 1Division of Nephrology, Endocrinology and Vascular Medicine, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai, 980-8574, Japan. k-n-0922@med.tohoku.ac.jp.

Scientific Reports
|January 10, 2018
PubMed

Insights

Indoxyl sulfate (IS) activates the (pro)renin receptor [(P)RR], promoting kidney fibrosis. Blocking (P)RR may treat kidney disease, and soluble (P)RR (s(P)RR) may serve as a fibrosis biomarker.

Area of Science:

  • Nephrology
  • Molecular Biology
  • Biochemistry

Background:

  • The (pro)renin receptor [(P)RR] plays a role in renal injury.
  • Indoxyl sulfate (IS), a uremic toxin, activates (P)RR and is linked to renal fibrosis, but the precise mechanisms are unclear.

Purpose of the Study:

  • To investigate the association between (P)RR and mesangial fibrosis in kidney disease.
  • To explore the role of the IS-(P)RR pathway in fibrotic processes.
  • To evaluate serum soluble (P)RR [s(P)RR] as a potential biomarker for mesangial fibrosis.

Main Methods:

  • In vitro studies using mouse mesangial cells (SV40 MES13) exposed to IS.
  • Investigating the effect of IS on (P)RR expression and fibrotic factors.
  • Utilizing (P)RR knockdown to assess its role in IS-induced fibrosis.
  • Analyzing the correlation between serum s(P)RR levels and clinical/pathological data in chronic kidney disease patients, particularly IgA nephropathy.

Main Results:

  • IS significantly upregulated (P)RR expression in mesangial cells.
  • IS-induced expression of fibrotic factors was attenuated by (P)RR knockdown.
  • IS increased matrix metalloproteinase 9 and tissue inhibitor of metalloproteinase 1 via the ERK1/2 pathway.
  • Serum s(P)RR levels correlated positively with serum IS and markers of mesangial injury.

Conclusions:

  • The IS-(P)RR-ERK1/2 pathway is implicated in mesangial fibrosis and matrix expansion.
  • (P)RR activation by IS contributes to the progression of kidney fibrosis.
  • Serum s(P)RR may serve as a valuable clinical biomarker for assessing mesangial fibrosis in kidney disease.

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