Abstract
Podocytes are highly differentiated epithelial cells wrapping glomerular capillaries to form the filtration barrier in kidneys. As such, podocyte injury or dysfunction is a critical pathogenic event in glomerular disease. Autophagy plays an important role in the maintenance of the homeostasis and function of podocytes. However, it is less clear whether and how autophagy contributes to podocyte injury in glomerular disease. Here, we have examined the role of autophagy in adriamycin-induced nephropathy, a classic model of glomerular disease. We show that autophagy was induced by adriamycin in cultured podocytes in vitro and in podocytes in mice. In cultured podocytes, activation of autophagy with rapamycin led to the suppression of adriamycin-induced apoptosis, whereas inhibition of autophagy with chloroquine enhanced podocyte apoptosis during adriamycin treatment. To determine the role of autophagy in vivo, we established an inducible podocyte-specific autophagy-related gene 7 knockout mouse model (Podo-Atg7-KO). Compared with wild-type littermates, Podo-Atg7-KO mice showed higher levels of podocyte injury, glomerulopathy, and proteinuria during adriamycin treatment. Together, these observations support an important role of autophagy in protecting podocytes under the pathological conditions of glomerular disease, suggesting the therapeutic potential of autophagy induction.
| Original language | English (US) |
|---|---|
| Pages (from-to) | F74-F84 |
| Journal | American Journal of Physiology - Renal Physiology |
| Volume | 313 |
| Issue number | 1 |
| DOIs | |
| State | Published - Jan 1 2017 |
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Keywords
- Adriamycin
- Apoptosis
- Autophagy
- Kidney
- Podocytes
- mTOR
ASJC Scopus subject areas
- Physiology
- Urology
Cite this
Autophagy is activated to protect against podocyte injury in adriamycin-induced nephropathy. / Yi, Mixuan; Zhang, Lei; Liu, Yu; Livingston, Man Jiang; Chen, Jiankang; Nahman, Norris Stanley; Liu, Fuyou; Dong, Zheng.
In: American Journal of Physiology - Renal Physiology, Vol. 313, No. 1, 01.01.2017, p. F74-F84.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Autophagy is activated to protect against podocyte injury in adriamycin-induced nephropathy
AU - Yi, Mixuan
AU - Zhang, Lei
AU - Liu, Yu
AU - Livingston, Man Jiang
AU - Chen, Jiankang
AU - Nahman, Norris Stanley
AU - Liu, Fuyou
AU - Dong, Zheng
PY - 2017/1/1
Y1 - 2017/1/1
N2 - Podocytes are highly differentiated epithelial cells wrapping glomerular capillaries to form the filtration barrier in kidneys. As such, podocyte injury or dysfunction is a critical pathogenic event in glomerular disease. Autophagy plays an important role in the maintenance of the homeostasis and function of podocytes. However, it is less clear whether and how autophagy contributes to podocyte injury in glomerular disease. Here, we have examined the role of autophagy in adriamycin-induced nephropathy, a classic model of glomerular disease. We show that autophagy was induced by adriamycin in cultured podocytes in vitro and in podocytes in mice. In cultured podocytes, activation of autophagy with rapamycin led to the suppression of adriamycin-induced apoptosis, whereas inhibition of autophagy with chloroquine enhanced podocyte apoptosis during adriamycin treatment. To determine the role of autophagy in vivo, we established an inducible podocyte-specific autophagy-related gene 7 knockout mouse model (Podo-Atg7-KO). Compared with wild-type littermates, Podo-Atg7-KO mice showed higher levels of podocyte injury, glomerulopathy, and proteinuria during adriamycin treatment. Together, these observations support an important role of autophagy in protecting podocytes under the pathological conditions of glomerular disease, suggesting the therapeutic potential of autophagy induction.
AB - Podocytes are highly differentiated epithelial cells wrapping glomerular capillaries to form the filtration barrier in kidneys. As such, podocyte injury or dysfunction is a critical pathogenic event in glomerular disease. Autophagy plays an important role in the maintenance of the homeostasis and function of podocytes. However, it is less clear whether and how autophagy contributes to podocyte injury in glomerular disease. Here, we have examined the role of autophagy in adriamycin-induced nephropathy, a classic model of glomerular disease. We show that autophagy was induced by adriamycin in cultured podocytes in vitro and in podocytes in mice. In cultured podocytes, activation of autophagy with rapamycin led to the suppression of adriamycin-induced apoptosis, whereas inhibition of autophagy with chloroquine enhanced podocyte apoptosis during adriamycin treatment. To determine the role of autophagy in vivo, we established an inducible podocyte-specific autophagy-related gene 7 knockout mouse model (Podo-Atg7-KO). Compared with wild-type littermates, Podo-Atg7-KO mice showed higher levels of podocyte injury, glomerulopathy, and proteinuria during adriamycin treatment. Together, these observations support an important role of autophagy in protecting podocytes under the pathological conditions of glomerular disease, suggesting the therapeutic potential of autophagy induction.
KW - Adriamycin
KW - Apoptosis
KW - Autophagy
KW - Kidney
KW - Podocytes
KW - mTOR
UR - http://www.scopus.com/inward/record.url?scp=85021861209&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85021861209&partnerID=8YFLogxK
U2 - 10.1152/ajprenal.00114.2017
DO - 10.1152/ajprenal.00114.2017
M3 - Article
C2 - 28404589
AN - SCOPUS:85021861209
VL - 313
SP - F74-F84
JO - American Journal of Physiology - Heart and Circulatory Physiology
JF - American Journal of Physiology - Heart and Circulatory Physiology
SN - 0363-6135
IS - 1
ER -