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

• DOI: 10.1016/j.apsb.2020.10.024
• Publication Date: 2020-11-05T17:57:06Z
• Authors: Xu Jing; Dandan Ren; Fei Gao; Ye Chen; Xiao Wu; Yue Han; Qingsheng Han; Liang Li; Xiaojie Wang; Wei Tang; Yan Zhang
• Keywords: Ponatinib

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 kidney, contributions mechanisms PDCD4 kidney injury (AKI) remained unclear. Using two murine AKI models including renal ischemia/reperfusion (IRI) cisplatin-induced AKI, we found deficiency markedly ameliorated dysfunction inflammatory mice. Consistently, upregulation was also confirmed kidneys from patients with biopsy tubular necrosis a retrospective cohort study. Moreover, overexpression Fgr, member tyrosine kinase family, dramatically aggravated counteracted protective effects We discovered FGR upregulated NOTCH1 expression through activating STAT3. Most importantly, further systemic administration ponatinib, inhibitor, significantly In summary, identified served as an important regulator, at least part, FGR/NOTCH1-mediated apoptosis inflammation Furthermore, our findings suggest ponatinib-mediated pharmacologic targeting this pathway had therapeutic potential for mitigating AKI.