2. Academic Validation
  3. HDAC6-mediated α-tubulin deacetylation suppresses autophagy and enhances motility of podocytes in diabetic nephropathy

HDAC6-mediated α-tubulin deacetylation suppresses autophagy and enhances motility of podocytes in diabetic nephropathy

  • J Cell Mol Med. 2020 Oct;24(19):11558-11572. doi: 10.1111/jcmm.15772.
Tiantian Liang 1,  Chunfang Qi 1 2,  Yuxiong Lai 1,  Jianteng Xie 1,  Huizhen Wang 1 3,  Li Zhang 1 3,  Ting Lin 1,  Menglei Jv 1 3,  Jing Li 1 3,  Yanhui Wang 3,  Yifan Zhang 1 3,  Zujiao Chen 1 3,  Xueqian Qiu 1 3,  Ruizhao Li 1,  Zhilian Li 1,  Zhiming Ye 1,  Shuangxin Liu 1,  Xinling Liang 1,  Wei Shi 1,  Wenjian Wang 1 2 3
Affiliations

Affiliations

  • 1 Division of Nephrology, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China.
  • 2 School of Medicine, South China University of Technology, Guangzhou, China.
  • 3 Southern Medical University, Guangzhou, China.
PMID: 32885602 DOI: 10.1111/jcmm.15772
Abstract

Histone deacetylase 6 (HDAC6) is the specific subtype of HDACs which preferentially located in the cytoplasm, and is crucial in Insulin signalling. However, the role of HDAC6 in type 2 diabetic nephropathy (DN) remains undefined. In current study, we observed that HDAC6 was markedly activated in the kidneys of type 2 diabetic patients and db/db mice with albuminuria, along with the advanced glycation end products (AGE)-treated podocytes. Selective inhibition of HDAC6 activity protected kidneys from hyperglycaemia in db/db mice. Notably, overexpressing HDAC6 inhibited Autophagy and promoted motility aside from the Apoptosis of podocytes exposed to AGE. We further determined that HDAC6 regulated the Autophagy partially by decreasing the acetylation of α-tubulin at the residue of lysine 40. In contrast, we confirmed that there was no interaction of HDAC6 with α-tubulin at the sites of lysine 112 and lysine 352. Consistently, inhibiting HDAC6 by siRNA or the selective inhibitor, tubacin, restored the Autophagy level and motility of podocytes and rescued podocytes from AGE stimulation. We provide strong evidence of an unexpected role of HDAC6 in the cascade that modulates podocytes Autophagy and motility, enlightening that HDAC6 may be a promising therapeutic target for DN treatment.

Keywords

autophagy; diabetic nephropathy; histone deacetylase 6; podocytes; α-tubulin.

Figures
Products
嗨！很高兴为您提供帮助！

尊敬的 MCE 客户您好，
请您选择所在区域，我们将转接对应客服为您服务！

热门区域

A

B

C

F

G

H

J

L

N

Q

S

T

X

Y

Z

热 A B C F G H J L N Q S T X Y Z