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http://ir.nhri.org.tw/handle/3990099045/12736
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| Title: | Tubular transcriptional co-activator with PDZ-binding motif protects against ischemic acute kidney injury |
| Authors: | Wu, CL;Chang, CC;Yang, TH;Tsai, AC;Wang, JL;Chang, CH;Tarng, DC |
| Contributors: | Institute of Cellular and Systems Medicine |
| Abstract: | Transcriptional co-activator with PDZ-binding motif (TAZ) is a key downstream effector of the Hippo tumor-suppressor pathway. The functions of TAZ in the kidney, especially in tubular epithelial cells, are not well-known. To elucidate the adaptive expression, protective effects on kidney injury, and signaling pathways of TAZ in response to acute kidney injury (AKI), we used in vitro (hypoxia-treated human renal proximal tubular epithelial cells [RPTECs]) and in vivo (mouse ischemia-reperfusion injury [IRI]) models of ischemic AKI. After ischemic AKI, TAZ was upregulated in RPTECs and the renal cortex or tubules. Upregulation of TAZ in RPTECs subjected to hypoxia was controlled by IKK/NF-κB signaling. TAZ overexpression attenuated hypoxic and oxidative injury, inhibited apoptosis and activation of p38 and JNK proteins, and promoted wound healing in an RPTEC monolayer. However, TAZ knockdown aggravated hypoxic injury, apoptosis, and activation of p38 and JNK signaling; delayed wound closure of an RPTEC monolayer; and promoted G0/G1 phase cell-cycle arrest. Chloroquine and verteporfin treatment produced similar results to TAZ overexpression and knockdown in RPTECs, respectively. Compared with vehicle-treated mice, chloroquine treatment increased TAZ in the renal cortex and tubules, improved renal function, and attenuated tubular injury and tubular apoptosis after renal IRI, whereas TAZ siRNA and verteporfin decreased TAZ in the renal cortex and tubules, deteriorated renal failure and tubular injury, and aggravated tubular apoptosis. Our findings indicate the renoprotective role of tubular TAZ in ischemic AKI. Drugs augmenting or suppressing TAZ in the kidney might be beneficial or deleterious to patients with AKI. |
| Date: | 2020-06-19 |
| Relation: | Clinical Science. 2020 Jun 19;134(13):1593-1612. |
| Link to: | http://dx.doi.org/10.1042/cs20200223 |
| JIF/Ranking 2023: | http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=0143-5221&DestApp=IC2JCR |
| Cited Times(WOS): | https://www.webofscience.com/wos/woscc/full-record/WOS:000548182200002 |
| Cited Times(Scopus): | https://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=85087433375 |
| Appears in Collections: | [張中和] 期刊論文
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| PUB32558891.pdf | | 17665Kb | Adobe PDF | 242 | View/Open |
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