Phosphate-induced renal fibrosis requires the prolyl isomerase Pin1

Zhong Jian Shen, Jie Hu, Kazuhiro Shiizaki, Makoto Kuro-O, James S. Malter

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Tubulo-interstitial fibrosis is a common, destructive endpoint for a variety of kidney diseases. Fibrosis is well correlated with the loss of kidney function in both humans and rodents. The identification of modulators of fibrosis could provide novel therapeutic approaches to reducing disease progression or severity. Here, we show that the peptidylprolyl isomerase Pin1 is an important molecular contributor that facilitates renal fibrosis in a well-characterized animal model. While wild-type mice fed a high phosphate diet (HPD) for 8-12 weeks developed calcium deposition, macrophage infiltration and extracellular matrix (ECM) accumulation in the kidney interstitium, Pin1 null mice showed significantly less pathology. The serum Pi in both WT and KO mice were significantly increased by the HPD, but the serum Ca was slightly decreased in KO compared to WT. In addition, both WT and KO HPD mice had less weight gain but exhibited normal organ mass (kidney, lung, spleen, liver and heart). Unexpectedly, renal function was not initially impaired in either genotype irrespective of the HPD. Our results suggest that diet containing high Pi induces rapid renal fibrosis before a significant impact on renal function and that Pin1 plays an important role in the fibrotic process.

Original languageEnglish (US)
Article numbere0150093
JournalPLoS One
Volume11
Issue number2
DOIs
StatePublished - Feb 1 2016

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Peptidylprolyl Isomerase
isomerases
Nutrition
fibrosis
Fibrosis
Phosphates
kidneys
phosphates
Kidney
renal function
Diet
diet
mice
peptidylprolyl isomerase
Macrophages
Pathology
kidney diseases
endpoints
Infiltration
disease course

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Phosphate-induced renal fibrosis requires the prolyl isomerase Pin1. / Shen, Zhong Jian; Hu, Jie; Shiizaki, Kazuhiro; Kuro-O, Makoto; Malter, James S.

In: PLoS One, Vol. 11, No. 2, e0150093, 01.02.2016.

Research output: Contribution to journalArticle

Shen, Zhong Jian ; Hu, Jie ; Shiizaki, Kazuhiro ; Kuro-O, Makoto ; Malter, James S. / Phosphate-induced renal fibrosis requires the prolyl isomerase Pin1. In: PLoS One. 2016 ; Vol. 11, No. 2.
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