Periostin promotes renal cyst growth and interstitial fibrosis in polycystic kidney disease

Darren P. Wallace, Corey White, Lyudmyla Savinkova, Emily Nivens, Gail A. Reif, Cibele S. Pinto, Archana Raman, Stephen C. Parnell, Simon Conway, Timothy A. Fields

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

In renal cystic diseases, sustained enlargement of fluid-filled cysts is associated with severe interstitial fibrosis and progressive loss of functioning nephrons. Periostin, a matricellular protein, is highly overexpressed in cyst-lining epithelial cells of autosomal-dominant polycystic disease kidneys (ADPKD) compared with normal tubule cells. Periostin accumulates in situ within the matrix subjacent to ADPKD cysts, binds to α V β 3 and α V β 5 integrins, and stimulates the integrin-linked kinase to promote cell proliferation. We knocked out periostin (Postn) in pcy/pcy mice, an orthologous model of nephronophthisis type 3, to determine whether periostin loss reduces PKD progression in a slowly progressive model of renal cystic disease. At 20 weeks of age, pcy/pcy:Postn-/- mice had a 34% reduction in kidney weight/body weight, a reduction in cyst number and total cystic area, a 69% reduction in phosphorylated S6, a downstream component of the mTOR pathway, and fewer proliferating cells in the kidneys compared with pcy/pcy:Postn +/+ mice. The pcy/pcy Postin knockout mice also had less interstitial fibrosis with improved renal function at 20 weeks and significantly longer survival (51.4 compared with 38.0 weeks). Thus, periostin adversely modifies the progression of renal cystic disease by promoting cyst epithelial cell proliferation, cyst enlargement, and interstitial fibrosis, all contributing to the decline in renal function and premature death.

Original languageEnglish
Pages (from-to)845-854
Number of pages10
JournalKidney International
Volume85
Issue number4
DOIs
StatePublished - 2014

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Polycystic Kidney Diseases
Cysts
Cystic Kidney Diseases
Fibrosis
Kidney
Autosomal Dominant Polycystic Kidney
Growth
N-terminal tetrapeptide cystatin C
Epithelial Cells
Cell Proliferation
Cyst Fluid
S 6
Premature Mortality
Nephrons
Knockout Mice
Integrins
Weight Loss
Body Weight
Weights and Measures
Proteins

Keywords

  • ADPKD
  • Integrin-linked kinase
  • Integrins
  • Osteoblast-specific factor 2
  • Proliferation

ASJC Scopus subject areas

  • Nephrology
  • Medicine(all)

Cite this

Wallace, D. P., White, C., Savinkova, L., Nivens, E., Reif, G. A., Pinto, C. S., ... Fields, T. A. (2014). Periostin promotes renal cyst growth and interstitial fibrosis in polycystic kidney disease. Kidney International, 85(4), 845-854. https://doi.org/10.1038/ki.2013.488

Periostin promotes renal cyst growth and interstitial fibrosis in polycystic kidney disease. / Wallace, Darren P.; White, Corey; Savinkova, Lyudmyla; Nivens, Emily; Reif, Gail A.; Pinto, Cibele S.; Raman, Archana; Parnell, Stephen C.; Conway, Simon; Fields, Timothy A.

In: Kidney International, Vol. 85, No. 4, 2014, p. 845-854.

Research output: Contribution to journalArticle

Wallace, DP, White, C, Savinkova, L, Nivens, E, Reif, GA, Pinto, CS, Raman, A, Parnell, SC, Conway, S & Fields, TA 2014, 'Periostin promotes renal cyst growth and interstitial fibrosis in polycystic kidney disease', Kidney International, vol. 85, no. 4, pp. 845-854. https://doi.org/10.1038/ki.2013.488
Wallace, Darren P. ; White, Corey ; Savinkova, Lyudmyla ; Nivens, Emily ; Reif, Gail A. ; Pinto, Cibele S. ; Raman, Archana ; Parnell, Stephen C. ; Conway, Simon ; Fields, Timothy A. / Periostin promotes renal cyst growth and interstitial fibrosis in polycystic kidney disease. In: Kidney International. 2014 ; Vol. 85, No. 4. pp. 845-854.
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