1. Roles for VEGF‐C/NRP–2 axis in regulating renal tubular epithelial cell survival and autophagy during serum deprivation
- Author
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Xiaoyan Chang, Ying Zhang, Conghui Zhang, Qian Yang, Yanyan Liu, Gang Xu, and Xinjun Liang
- Subjects
Serum ,0301 basic medicine ,autophagy ,NRP–2 ,Programmed cell death ,Cell Survival ,medicine.medical_treatment ,Vascular Endothelial Growth Factor C ,Clinical Biochemistry ,Cell ,Biology ,serum deprivation ,survival ,Biochemistry ,Cell Line ,03 medical and health sciences ,0302 clinical medicine ,medicine ,Animals ,Viability assay ,Receptor ,vascular endothelial growth factor C (VEGF‐C) ,Research Articles ,Kinase ,Growth factor ,Autophagy ,Epithelial Cells ,Cell Biology ,General Medicine ,Neuropilin-2 ,Rats ,Cell biology ,Kidney Tubules ,030104 developmental biology ,medicine.anatomical_structure ,Cell culture ,030220 oncology & carcinogenesis ,Research Article ,Signal Transduction - Abstract
Vascular endothelial growth factor C (VEGF-C) is an angiogenic and lymphangiogenic growth factor. Recent research has revealed the role for VEGF-C in regulating autophagy by interacting with a nontyrosine kinase receptor, neuropilin-2 (NRP-2). However, whether VEGF-C participates in regulating cell survival and autophagy in renal proximal tubular cells is unknown. To address this question, we employed a cell modal of serum deprivation to verify the role of VEGF-C and its receptor NRP-2 in regulating cell survival and autophagy in NRK52E cell lines. The results show that VEGF-C rescued the loss of cell viability induced by serum deprivation in a concentration-dependent manner. Furthermore, endogenous VEGF-C was knocked down in NRK52E cells by using specific small-interfering RNAs (siRNA), cells were more sensitive to serum deprivation-induced cell death. A similar increase in cell death rate was observed following NRP-2 depletion in serum-starved NRK52E cells. Autophagy activity in serum-starved NRK52E cells was confirmed by western blot analysis of microtubule-associated protein-1 chain 3 (LC3), immunofluorescence staining of endogenous LC3, and the formation of autophagosomes by electron microscopy. VEGF-C or NRP-2 depletion further increased LC3 expression induced by serum deprivation, suggesting that VEGF-C and NRP-2 were involved in controlling autophagy in NRK52E cells. We further performed autophagic flux experiments to identify that VEGF-C promotes the activation of autophagy in serum-starved NRK52E cells. Together, these results suggest for the first time that VEGF-C/NRP-2 axis promotes survival and autophagy in NRK52E cells under serum deprivation condition. SIGNIFICANCE OF THE STUDY: More researchers had focused on the regulation of autophagy in kidney disease. The effect of VEGF-C on cell death and autophagy in renal epithelial cells has not been examined. We first identified the VEGF-C as a regulator of cell survival and autophagy in NRK52E cell lines. And VEGF-C/NRP-2 may mediate autophagy by regulating the phosphorylation of 4EBP1 and P70S6K. VEGF-C treatment may be identified as a therapeutic target in renal injury repair due to its capacity to promote tubular cell survival in the future.
- Published
- 2019