Klotho plays a protective role against glomerular hypertrophy in a cell cycle-dependent manner in diabetic nephropathy

Hyung Jung Oh, Bo Young Nam, Meiyan Wu, Seonghun Kim, Jimin Park, Sukyung Kang, Jung Tak Park, TaeHyun Yoo, Shin-Wook Kang, SeungHyeok Han

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Klotho plays a protective role against glomerular hypertrophy in a cell cycle-dependent manner in diabetic nephropathy. Am J Physiol Renal Physiol 315: F791–F805, 2018. First published April 11, 2018; doi:10.1152/ajprenal.00462.2017.— There are few studies on the effect of klotho on podocytes in diabetic nephropathy. Thus, we tested whether klotho exerts a protective effect against glomerular injury in diabetes. Mouse podocytes were cultured in media containing 5.6 or 30 mM glucose(HG) with or without 200 pM of recombinant klotho (rKL). Additionally, 32 mice were injected intraperitoneally with either diluent(n = 16, C) or with streptozotocin (n = 16, DM). Control and diabetic mice underwent sham operation and unilateral nephrectomy, respectively. Eight mice from each control and DM group were treated daily with 10 μg·kg−1·day−1 of rKL, using an osmotic minipump. Klotho was expressed in podocytes, and its expression was dependent on peroxisome proliferator-activateed receptor-γ (PPARγ). HG treatment increased the expression of cell cycle-related and apoptotic markers, and these were significantly attenuated by rKL; rKL inhibited the extracellular signal-regulated protein kinase-1/2 and p38 signaling pathways in HG-induced podocyte injury. However, siRNA against klotho gene in HG-treated podocytes failed to aggravate cell cycle arrest and apoptosis. When HG-treated podocytes were incubated in the high-klotho-conditioned medium from tubular epithelial cells, cell injury was significantly attenuated. This effect was not observed when klotho was inhibited by siRNA. In vivo, the expressions of cell cycle-related and apoptotic markers were increased in diabetic mice compared with controls, which were significantly decreased by rKL. Glomerular hypertrophy (GH) and increased profibrotic markers were significantly alleviated after rKL administration. These results showed that klotho was expressed in glomerular podocytes that and its expression was regulated by PPARγ. Additionally, administration of rKL attenuated GH via a cell cycle-dependent mechanism and decreased apoptosis.

Original languageEnglish
Pages (from-to)F791-F805
JournalAmerican Journal of Physiology - Renal Physiology
Volume315
Issue number4
DOIs
Publication statusPublished - 2018 Oct 1

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Podocytes
Diabetic Nephropathies
Hypertrophy
Cell Cycle
Peroxisome Proliferator-Activated Receptors
Small Interfering RNA
Wounds and Injuries
Apoptosis
Mitogen-Activated Protein Kinase 3
Streptozocin
Conditioned Culture Medium
Cell Cycle Checkpoints
Nephrectomy
Protein Kinases
Epithelial Cells
Kidney
Glucose
Control Groups
Genes

All Science Journal Classification (ASJC) codes

  • Physiology
  • Urology

Cite this

Oh, Hyung Jung ; Nam, Bo Young ; Wu, Meiyan ; Kim, Seonghun ; Park, Jimin ; Kang, Sukyung ; Park, Jung Tak ; Yoo, TaeHyun ; Kang, Shin-Wook ; Han, SeungHyeok. / Klotho plays a protective role against glomerular hypertrophy in a cell cycle-dependent manner in diabetic nephropathy. In: American Journal of Physiology - Renal Physiology. 2018 ; Vol. 315, No. 4. pp. F791-F805.
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Klotho plays a protective role against glomerular hypertrophy in a cell cycle-dependent manner in diabetic nephropathy. / Oh, Hyung Jung; Nam, Bo Young; Wu, Meiyan; Kim, Seonghun; Park, Jimin; Kang, Sukyung; Park, Jung Tak; Yoo, TaeHyun; Kang, Shin-Wook; Han, SeungHyeok.

In: American Journal of Physiology - Renal Physiology, Vol. 315, No. 4, 01.10.2018, p. F791-F805.

Research output: Contribution to journalArticle

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AU - Oh, Hyung Jung

AU - Nam, Bo Young

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AU - Kim, Seonghun

AU - Park, Jimin

AU - Kang, Sukyung

AU - Park, Jung Tak

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AU - Kang, Shin-Wook

AU - Han, SeungHyeok

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