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BMC Nephrology
Published in: BMC Nephrology 1/2016

Open Access 01-12-2016 | Research article

RhoA deficiency disrupts podocyte cytoskeleton and induces podocyte apoptosis by inhibiting YAP/dendrin signal

Authors: Zongshun Huang, Li Zhang, Yuanhan Chen, Hong Zhang, Chunping Yu, Fangjian Zhou, Zhiling Zhang, Lijuan Jiang, Ruizhao Li, Jianchao Ma, Zhuo Li, Yuxiong Lai, Ting Lin, Xinchen Zhao, Qianmei Zhang, Bin Zhang, Zhiming Ye, Shuangxin Liu, Wenjian Wang, Xinling Liang, Ruyi Liao, Wei Shi

Published in: BMC Nephrology | Issue 1/2016

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Abstract

Background

Podocyte apoptosis is a major mechanism that leads to proteinuria in many kidney diseases. However, the concert mechanisms that cause podocyte apoptosis in these kidney diseases are not fully understood. RhoA is one of Rho GTPases that has been well studied and plays a key role in regulating cytoskeletal architecture. Previous study showed that insufficient RhoA could result in rat aortic smooth muscle cell apoptosis. However, whether RhoA is involved in podocyte apoptosis remains unknown.

Methods

Culture podocytes were treated with LPS, ADR or siRNA for 48 h before harvest. Subcellular immunoblotting, qRT-PCR, immunofluorescence and flow cytometry were used to exam the expression and function of RhoA or YAP in podocytes.

Results

We found that the expression of RhoA and its activity were significantly decreased in LPS or ADR-injured podocytes, accompanying loss of stress fibers and increased cell apoptosis. Knocking down RhoA or its downstream effector mDia expression by siRNA also caused loss of stress fibers and podocyte apoptosis. Moreover, our results further demonstrated that RhoA deficiency could reduce the mRNA and protein expression of YAP, which had been regarded as an anti-apoptosis protein in podocyte. Silenced dendrin expression significantly abolished RhoA, mDia or YAP deficiency-induced podocyte apoptosis.

Conclusion

RhoA deficiency could disrupt podocyte cytoskeleton and induce podocyte apoptosis by inhibiting YAP/dendrin signal. RhoA/mDia/YAP/dendrin signal pathway may potentially play an important role in regulating podocyte apoptosis. Maintaining necessary RhoA would be one potent way to prevent proteinuria kidney diseases.
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Metadata
Title
RhoA deficiency disrupts podocyte cytoskeleton and induces podocyte apoptosis by inhibiting YAP/dendrin signal
Authors
Zongshun Huang
Li Zhang
Yuanhan Chen
Hong Zhang
Chunping Yu
Fangjian Zhou
Zhiling Zhang
Lijuan Jiang
Ruizhao Li
Jianchao Ma
Zhuo Li
Yuxiong Lai
Ting Lin
Xinchen Zhao
Qianmei Zhang
Bin Zhang
Zhiming Ye
Shuangxin Liu
Wenjian Wang
Xinling Liang
Ruyi Liao
Wei Shi
Publication date
01-12-2016
Publisher
BioMed Central
Published in
BMC Nephrology / Issue 1/2016
Electronic ISSN: 1471-2369
DOI
https://doi.org/10.1186/s12882-016-0287-6

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