Gene deficiency or pharmacological inhibition of PDCD4-mediated FGR signaling protects against acute kidney injury.

Xu Jing; Dandan Ren; Fei Gao; Ye Chen; Xiao WU; Yue Han; Qingsheng Han; Liang LI; Xiaojie Wang; Wei Tang; Yan Zhang

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Gene deficiency or pharmacological inhibition of PDCD4-mediated FGR signaling protects against acute kidney injury.

Author: Xu JING ¹ ; Dandan REN ¹ ; Fei GAO ² ; Ye CHEN ¹ ; Xiao WU ² ; Yue HAN ¹ ; Qingsheng HAN ¹ ; Liang LI ¹ ; Xiaojie WANG ¹ ; Wei TANG ³ ; Yan ZHANG ¹
Author Information

1. Department of Pharmacology, School of Basic Medical Science, Shandong University, Jinan 250012, China.
2. The Key Laboratory of Cardiovascular Remodeling and Function Research, Department of Cardiology, Qilu Hospital of Shandong University, Jinan 250012, China.
3. Department of Microbiology, School of Basic Medical Science, Shandong University, Jinan 250012, China.
Publication Type:Journal Article
Keywords: Acute kidney injury; Cell death; FGR; Inflammation; Ischemia–reperfusion injury; NOTCH1; PDCD4; Tyrosine kinase
From: Acta Pharmaceutica Sinica B 2021;11(2):394-405
CountryChina
Language:English
Abstract: Recent studies have shown that programmed cell death 4 (PDCD4) modulates distinct signal transduction pathways in different pathological conditions. Despite acute and chronic immune responses elicited by ischemia contributing to the functional deterioration of the kidney, the contributions and mechanisms of PDCD4 in acute kidney injury (AKI) have remained unclear. Using two murine AKI models including renal ischemia/reperfusion injury (IRI) and cisplatin-induced AKI, we found that PDCD4 deficiency markedly ameliorated renal dysfunction and inflammatory responses in AKI mice. Consistently, upregulation of PDCD4 was also confirmed in the kidneys from patients with biopsy confirmed acute tubular necrosis from a retrospective cohort study. Moreover, we found that overexpression of