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 language | English |
|---|---|
| Pages (from-to) | F791-F805 |
| Journal | American Journal of Physiology - Renal Physiology |
| Volume | 315 |
| Issue number | 4 |
| DOIs | |
| Publication status | Published - 2018 Oct |
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All Science Journal Classification (ASJC) codes
- Physiology
- Urology
Cite this
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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, Tae Hyun; Kang, Shin Wook; Han, Seung Hyeok.
In: American Journal of Physiology - Renal Physiology, Vol. 315, No. 4, 10.2018, p. F791-F805.Research output: Contribution to journal › Article
TY - JOUR
T1 - Klotho plays a protective role against glomerular hypertrophy in a cell cycle-dependent manner in diabetic nephropathy
AU - Oh, Hyung Jung
AU - Nam, Bo Young
AU - Wu, Meiyan
AU - Kim, Seonghun
AU - Park, Jimin
AU - Kang, Sukyung
AU - Park, Jung Tak
AU - Yoo, Tae Hyun
AU - Kang, Shin Wook
AU - Han, Seung Hyeok
PY - 2018/10
Y1 - 2018/10
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85053617141&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85053617141&partnerID=8YFLogxK
U2 - 10.1152/ajprenal.00462.2017
DO - 10.1152/ajprenal.00462.2017
M3 - Article
C2 - 29638159
AN - SCOPUS:85053617141
VL - 315
SP - F791-F805
JO - American Journal of Physiology - Renal Physiology
JF - American Journal of Physiology - Renal Physiology
SN - 1931-857X
IS - 4
ER -