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http://dx.doi.org/10.4062/biomolther.2019.214

Fyn Kinase: A Potential Therapeutic Target in Acute Kidney Injury  

Uddin, Md Jamal (Graduate School of Pharmaceutical Sciences, College of Pharmacy, Ewha Womans University)
Dorotea, Debra (Graduate School of Pharmaceutical Sciences, College of Pharmacy, Ewha Womans University)
Pak, Eun Seon (Graduate School of Pharmaceutical Sciences, College of Pharmacy, Ewha Womans University)
Ha, Hunjoo (Graduate School of Pharmaceutical Sciences, College of Pharmacy, Ewha Womans University)
Publication Information
Biomolecules & Therapeutics / v.28, no.3, 2020 , pp. 213-221 More about this Journal
Abstract
Acute kidney injury (AKI) is a common disease with a complex pathophysiology which significantly contributes to the development of chronic kidney disease and end stage kidney failure. Preventing AKI can consequently reduce mortality, morbidity, and healthcare burden. However, there are no effective drugs in use for either prevention or treatment of AKI. Developing therapeutic agents with pleiotropic effects covering multiple pathophysiological pathways are likely to be more effective in attenuating AKI. Fyn, a non-receptor tyrosine kinase, has been acknowledged to integrate multiple injurious stimuli in the kidney. Limited studies have shown increased Fyn transcription level and activation under experimental AKI. Activated Fyn kinase propagates various downstream signaling pathways associated to the progression of AKI, such as oxidative stress, inflammation, endoplasmic reticulum stress, as well as autophagy dysfunction. The versatility of Fyn kinase in mediating various pathophysiological pathways suggests that its inhibition can be a potential strategy in attenuating AKI.
Keywords
Fyn kinase; Acute kidney injury; Inflammation; Oxidative stress; ER stress; Autophagy;
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1 Wu, H., Shi, Y., Deng, X., Su, Y., Du, C., Wei, J., Ren, Y., Wu, M., Hou, Y. and Duan, H. (2015) Inhibition of c-Src/p38 MAPK pathway ameliorates renal tubular epithelial cells apoptosis in db/db mice. Mol. Cell. Endocrinol. 417, 27-35.   DOI
2 Davidson, D., Chow, L. M., Fournel, M. and Veillette, A. (1992) Differential regulation of T cell antigen responsiveness by isoforms of the src-related tyrosine protein kinase p59fyn. J. Exp. Med. 175, 1483-1492.   DOI
3 Davidson, D., Viallet, J. and Veillette, A. (1994) Unique catalytic properties dictate the enhanced function of p59fynT, the hemopoietic cell-specific isoform of the Fyn tyrosine protein kinase, in T cells. Mol. Cell. Biol. 14, 4554-4564.   DOI
4 Du, T., Zou, X., Cheng, J., Wu, S., Zhong, L., Ju, G., Zhu, J., Liu, G., Zhu, Y. and Xia, S. (2013) Human Wharton's jelly-derived mesenchymal stromal cells reduce renal fibrosis through induction of native and foreign hepatocyte growth factor synthesis in injured tubular epithelial cells. Stem Cell Res. Ther. 4, 59.   DOI
5 Fan, Y., Xiao, W., Lee, K., Salem, F., Wen, J., He, L., Zhang, J., Fei, Y., Cheng, D., Bao, H., Liu, Y., Lin, F., Jiang, G., Guo, Z., Wang, N. and He, J. C. (2017) Inhibition of reticulon-1a-mediated endoplasmic reticulum stress in early aki attenuates renal fibrosis development. J. Am. Soc. Nephrol. 28, 2007-2021.   DOI
6 Gallagher, K. M., O'Neill, S., Harrison, E. M., Ross, J. A., Wigmore, S. J. and Hughes, J. (2017) Recent early clinical drug development for acute kidney injury. Expert Opin. Investig. Drugs 26, 141-154.   DOI
7 Gao, X., Fu, L., Xiao, M., Xu, C., Sun, L., Zhang, T., Zheng, F. and Mei, C. (2012) The nephroprotective effect of tauroursodeoxycholic acid on ischaemia/reperfusion-induced acute kidney injury by inhibiting endoplasmic reticulum stress. Basic Clin. Pharmacol. Toxicol. 111, 14-23.   DOI
8 Goldsmith, J. F., Hall, C. G. and Atkinson, T. P. (2002) Identification of an alternatively spliced isoform of the fyn tyrosine kinase. Biochem. Biophys. Res.Commun. 298, 501-504.   DOI
9 Mkaddem, S. B., Murua, A., Flament, H., Titeca-Beauport, D., Bounaix, C., Danelli, L., Launay, P., Benhamou, M., Blank, U., Daugas, E., Charles, N. and Monteiro, R. C. (2017) Lyn and Fyn function as molecular switches that control immunoreceptors to direct homeostasis or inflammation. Nat. Commun. 8, 246.   DOI
10 Miyata, T., Suzuki, N. and van Ypersele de Strihou, C. (2013) Diabetic nephropathy: are there new and potentially promising therapies targeting oxygen biology? Kidney Int. 84, 693-702.   DOI
11 Moran, M. F., Koch, C. A., Anderson, D., Ellis, C., England, L., Martin, G. S. and Pawson, T. (1990) Src homology region 2 domains direct protein-protein interactions in signal transduction. Proc. Natl. Acad. Sci. U.S.A. 87, 8622-8626.   DOI
12 Ogbadu, J., Singh, G. and Aggarwal, D. (2019) Factors affecting the transition of acute kidney injury to chronic kidney disease: Potential mechanisms and future perspectives. Eur. J. Pharmacol. 865, 172711.   DOI
13 Pal, R., Palmieri, M., Chaudhury, A., Klisch, T. J., di Ronza, A., Neilson, J. R., Rodney, G. G. and Sardiello, M. (2018) Src regulates amino acid-mediated mTORC1 activation by disrupting GATOR1-Rag GTPase interaction. Nat. Commun. 9, 4351.   DOI
14 Yamada, E., Okada, S., Bastie, C. C., Vatish, M., Nakajima, Y., Shibusawa, R., Ozawa, A., Pessin, J. E. and Yamada, M. (2016) Fyn phosphorylates AMPK to inhibit AMPK activity and AMP-dependent activation of autophagy. Oncotarget 7, 74612-74629.   DOI
15 Pal, R., Palmieri, M., Loehr, J. A., Li, S., Abo-Zahrah, R., Monroe, T. O., Thakur, P. B., Sardiello, M. and Rodney, G. G. (2014) Src-dependent impairment of autophagy by oxidative stress in a mouse model of Duchenne muscular dystrophy. Nat. Commun. 5, 4425.   DOI
16 Panicker, N., Saminathan, H., Jin, H., Neal, M., Harischandra, D. S., Gordon, R., Kanthasamy, K., Lawana, V., Sarkar, S., Luo, J., Anantharam, V., Kanthasamy, A. G. and Kanthasamy, A. (2015) Fyn kinase regulates microglial neuroinflammatory responses in cell culture and animal models of parkinson's disease. J. Neurosci. 35, 10058-10077.   DOI
17 Xiong, C., Zang, X., Zhou, X., Liu, L., Masucci, M. V., Tang, J., Li, X., Liu, N., Bayliss, G., Zhao, T. C. and Zhuang, S. (2017) Pharmacological inhibition of Src kinase protects against acute kidney injury in a murine model of renal ischemia/reperfusion. Oncotarget 8, 31238-31253.   DOI
18 Xu, Y., Guo, M., Jiang, W., Dong, H., Han, Y., An, X. F. and Zhang, J. (2016) Endoplasmic reticulum stress and its effects on renal tubular cells apoptosis in ischemic acute kidney injury. Ren. Fail. 38, 831-837.   DOI
19 Yamada, E., Bastie, C. C., Koga, H., Wang, Y., Cuervo, A. M. and Pessin, J. E. (2012) Mouse skeletal muscle fiber-type-specific macroautophagy and muscle wasting are regulated by a Fyn/STAT3/ Vps34 signaling pathway. Cell Rep. 1, 557-569.   DOI
20 Yamada, E., Pessin, J. E., Kurland, I. J., Schwartz, G. J. and Bastie, C. C. (2010) Fyn-dependent regulation of energy expenditure and body weight is mediated by tyrosine phosphorylation of LKB1. Cell Metab. 11, 113-124.   DOI
21 Yan, Y., Ma, L., Zhou, X., Ponnusamy, M., Tang, J., Zhuang, M.A., Tolbert, E., Bayliss, G., Bai, J. and Zhuang, S. (2016) Src inhibition blocks renal interstitial fibroblast activation and ameliorates renal fibrosis. Kidney Int. 89, 68-81.   DOI
22 Jelic, D., Mildner, B., Kostrun, S., Nujic, K., Verbanac, D., Culic, O., Antolovic, R. and Brandt, W. (2007) Homology modeling of human Fyn kinase structure: discovery of rosmarinic acid as a new Fyn kinase inhibitor and in silico study of its possible binding modes. J. Med. Chem. 50, 1090-1100.   DOI
23 Yang, C., Kaushal, V., Shah, S. V. and Kaushal, G. P. (2008) Autophagy is associated with apoptosis in cisplatin injury to renal tubular epithelial cells. Am. J. Physiol. Renal Physiol. 294, 777-787.   DOI
24 Yang, L., Humphreys, B. D. and Bonventre, J. V. (2011) Pathophysiology of acute kidney injury to chronic kidney disease: maladaptive repair. Contrib. Nephrol. 174, 149-155.   DOI
25 Abram, C. L. and Lowell, C. A. (2008) The diverse functions of Src family kinases in macrophages. Front. Biosci. 13, 4426-4450.   DOI
26 Hsiao, H. W., Tsai, K. L., Wang, L. F., Chen, Y. H., Chiang, P. C., Chuang, S. M. and Hsu, C. (2012) The decline of autophagy contributes to proximal tubular dysfunction during sepsis. Shock 37, 289-296.   DOI
27 Huang, C., Bruggeman, L. A., Hydo, L. M. and Miller, R. T. (2012) Shear stress induces cell apoptosis via a c-Src-phospholipase D-mTOR signaling pathway in cultured podocytes. Exp. Cell Res. 318, 1075-1085.   DOI
28 Alers, S., Loffler, A. S., Wesselborg, S. and Stork, B. (2012) Role of AMPK-mTOR-Ulk1/2 in the regulation of autophagy: cross talk, shortcuts, and feedbacks. Mol. Cell. Biol. 32, 2-11.   DOI
29 Jain, A. K. and Jaiswal, A. K. (2007) GSK-3beta acts upstream of Fyn kinase in regulation of nuclear export and degradation of NF-E2 related factor 2. J. Biol. Chem. 282, 16502-16510.   DOI
30 Jang, H. R. and Rabb, H. (2009) The innate immune response in ischemic acute kidney injury. Clin. Immunol. 130, 41-50.   DOI
31 Jiang, M., Liu, K., Luo, J. and Dong, Z. (2010) Autophagy is a renoprotective mechanism during in vitro hypoxia and in vivo ischemiareperfusion injury. Am. J. Pathol. 176, 1181-1192.   DOI
32 Kato, H., Nakajima, S., Saito, Y., Takahashi, S., Katoh, R. and Kitamura, M. (2012) mTORC1 serves ER stress-triggered apoptosis via selective activation of the IRE1-JNK pathway. Cell Death Differ. 19, 310-320.   DOI
33 Keegan, R. F. and Webb, C. B. (2010) Oxidative stress and neutrophil function in cats with chronic renal failure. J. Vet. Intern. Med. 24, 514-519.   DOI
34 Kim, J., Kundu, M., Viollet, B. and Guan, K. L. (2011) AMPK and mTOR regulate autophagy through direct phosphorylation of Ulk1. Nat. Cell Biol. 13, 132-141.   DOI
35 Rizvi, F., Shukla, S. and Kakkar, P. (2014) Essential role of PH domain and leucine-rich repeat protein phosphatase 2 in Nrf2 suppression via modulation of Akt/GSK3beta/Fyn kinase axis during oxidative hepatocellular toxicity. Cell Death Dis. 5, e1153.   DOI
36 Patschan, D., Schwarze, K., Henze, E., Hoffmann, J. C., Patschan, S., Ritter, O. and Muller, G. A. (2019) Acute kidney injury-associated systemic inflammation is aggravated in insulin-dependent diabetes mellitus. J. Clin. Med. Res. 11, 720-723.   DOI
37 Rajasekaran, K., Kumar, P., Schuldt, K. M., Peterson, E. J., Vanhaesebroeck, B., Dixit, V., Thakar, M. S. and Malarkannan, S. (2013) Signaling by Fyn-ADAP via the Carma1-Bcl-10-MAP3K7 signalosome exclusively regulates inflammatory cytokine production in NK cells. Nat. Immunol. 14, 1127-1136.   DOI
38 Rana, A., Sathyanarayana, P. and Lieberthal, W. (2001) Role of apoptosis of renal tubular cells in acute renal failure: therapeutic implications. Apoptosis 6, 83-102.   DOI
39 Resh, M. D. (1998) Fyn, a Src family tyrosine kinase. Int. J. Biochem. Cell Biol. 30, 1159-1162.   DOI
40 Rifkin, D. E., Coca, S. G. and Kalantar-Zadeh, K. (2012) Does AKI truly lead to CKD? J. Am. Soc. Nephrol. 23, 979-984.   DOI
41 Roskoski, R., Jr. (2015) Src protein-tyrosine kinase structure, mechanism, and small molecule inhibitors. Pharmacol. Res. 94, 9-25.   DOI
42 Saito, Y. D., Jensen, A. R., Salgia, R. and Posadas, E. M. (2010) Fyn: a novel molecular target in cancer. Cancer 116, 1629-1637.   DOI
43 Saminathan, H., Asaithambi, A., Anantharam, V., Kanthasamy, A. G. and Kanthasamy, A. (2011) Environmental neurotoxic pesticide dieldrin activates a non receptor tyrosine kinase to promote PKCdelta-mediated dopaminergic apoptosis in a dopaminergic neuronal cell model. Neurotoxicology 32, 567-577.   DOI
44 Ardura, J. A., Rayego-Mateos, S., Ramila, D., Ruiz-Ortega, M. and Esbrit, P. (2010) Parathyroid hormone-related protein promotes epithelial-mesenchymal transition. J. Am. Soc. Nephrol. 21, 237-248.   DOI
45 Andrade-Oliveira, V., Foresto-Neto, O., Watanabe, I. K. M., Zatz, R. and Camara, N. O. S. (2019) Inflammation in renal diseases: new and old players. Front. Pharmacol. 10, 1192.   DOI
46 Anuranjani and Bala, M. (2014) Concerted action of Nrf2-ARE pathway, MRN complex, HMGB1 and inflammatory cytokines - implication in modification of radiation damage. Redox Biol. 2, 832-846.   DOI
47 Appleby, M. W., Gross, J. A., Cooke, M. P., Levin, S. D., Qian, X. and Perlmutter, R. M. (1992) Defective T cell receptor signaling in mice lacking the thymic isoform of p59fyn. Cell 70, 751-763.   DOI
48 Bailly-Maitre, B., Fondevila, C., Kaldas, F., Droin, N., Luciano, F., Ricci, J. E., Croxton, R., Krajewska, M., Zapata, J. M., Kupiec-Weglinski, J. W., Farmer, D. and Reed, J. C. (2006) Cytoprotective gene bi-1 is required for intrinsic protection from endoplasmic reticulum stress and ischemia-reperfusion injury. Proc. Natl. Acad. Sci. U.S.A. 103, 2809-2814.   DOI
49 Bastie, C. C., Zong, H., Xu, J., Busa, B., Judex, S., Kurland, I. J. and Pessin, J. E. (2007) Integrative metabolic regulation of peripheral tissue fatty acid oxidation by the SRC kinase family member Fyn. Cell Metab. 5, 371-381.   DOI
50 Basile, D. P., Anderson, M. D. and Sutton, T. A. (2012) Pathophysiology of acute kidney injury. Compr. Physiol. 2, 1303-1353.   DOI
51 Bellomo, R., Ronco, C., Kellum, J. A., Mehta, R. L. and Palevsky, P. (2004) Acute renal failure - definition, outcome measures, animal models, fluid therapy and information technology needs: the Second International Consensus Conference of the Acute Dialysis Quality Initiative (ADQI) Group. Crit. Care 8, 204-212.   DOI
52 Lambert, M. P., Barlow, A. K., Chromy, B. A., Edwards, C., Freed, R., Liosatos, M., Morgan, T. E., Rozovsky, I., Trommer, B., Viola, K. L., Wals, P., Zhang, C., Finch, C. E., Krafft, G. A. and Klein, W. L. (1998) Diffusible, nonfibrillar ligands derived from Abeta1-42 are potent central nervous system neurotoxins. Proc. Natl. Acad. Sci. U.S.A. 95, 6448-6453.   DOI
53 Kim, S., Joe, Y., Kim, H. J., Kim, Y. S., Jeong, S. O., Pae, H. O., Ryter, S. W., Surh, Y. J. and Chung, H. T. (2015) Endoplasmic reticulum stress-induced IRE1alpha activation mediates cross-talk of GSK-3beta and XBP-1 to regulate inflammatory cytokine production. J. Immunol. 194, 4498-4506.   DOI
54 Koo, J. H., Lee, W. H., Lee, C. G. and Kim, S. G. (2012) Fyn inhibition by cycloalkane-fused 1,2-dithiole-3-thiones enhances antioxidant capacity and protects mitochondria from oxidative injury. Mol. Pharmacol. 82, 27-36.   DOI
55 Kroemer, G., Marino, G. and Levine, B. (2010) Autophagy and the integrated stress response. Mol. Cell 40, 280-293.   DOI
56 Lawson, J., Elliott, J., Wheeler-Jones, C., Syme, H. and Jepson, R. (2015) Renal fibrosis in feline chronic kidney disease: known mediators and mechanisms of injury. Vet. J. 203, 18-26.   DOI
57 Lee, T. W., Kwon, H., Zong, H., Yamada, E., Vatish, M., Pessin, J. E. and Bastie, C. C. (2013) Fyn deficiency promotes a preferential increase in subcutaneous adipose tissue mass and decreased visceral adipose tissue inflammation. Diabetes 62, 1537-1546.   DOI
58 Lewington, A. J., Cerda, J. and Mehta, R. L. (2013) Raising awareness of acute kidney injury: a global perspective of a silent killer. Kidney Int. 84, 457-467.   DOI
59 Li, B., Liu, S., Miao, L. and Cai, L. (2012) Prevention of diabetic complications by activation of Nrf2: diabetic cardiomyopathy and nephropathy. Exp. Diabetes Res. 2012, 216512.
60 Sanchez, A. M., Candau, R. B., Csibi, A., Pagano, A. F., Raibon, A. and Bernardi, H. (2012) The role of AMP-activated protein kinase in the coordination of skeletal muscle turnover and energy homeostasis. Am. J. Physiol. Cell Physiol. 303, 475-485.
61 Seo, H. Y., Jeon, J. H., Jung, Y. A., Jung, G. S., Lee, E. J., Choi, Y. K., Park, K. G., Choe, M. S., Jang, B. K., Kim, M. K. and Lee, I. K. (2016) Fyn deficiency attenuates renal fibrosis by inhibition of phospho-STAT3. Kidney Int. 90, 1285-1297.   DOI
62 Santosa, D., Castoldi, M., Paluschinski, M., Sommerfeld, A. and Haussinger, D. (2015) Hyperosmotic stress activates the expression of members of the miR-15/107 family and induces downregulation of anti-apoptotic genes in rat liver. Sci. Rep. 5, 12292.   DOI
63 Schenone, S., Brullo, C., Musumeci, F., Biava, M., Falchi, F. and Botta, M. (2011) Fyn kinase in brain diseases and cancer: the search for inhibitors. Curr. Med. Chem. 18, 2921-2942.   DOI
64 Sengupta, S., Peterson, T. R. and Sabatini, D. M. (2010) Regulation of the mTOR complex 1 pathway by nutrients, growth factors, and stress. Mol. Cell 40, 310-322.   DOI
65 Shang, G., Tang, X., Gao, P., Guo, F., Liu, H., Zhao, Z., Chen, Q., Jiang, T., Zhang, N. and Li, H. (2015) Sulforaphane attenuation of experimental diabetic nephropathy involves GSK-3 beta/Fyn/Nrf2 signaling pathway. J. Nutr. Biochem. 26, 596-606.   DOI
66 Sugie, K., Jeon, M. S. and Grey, H. M. (2004) Activation of naive CD4 T cells by anti-CD3 reveals an important role for Fyn in Lck-mediated signaling. Proc. Natl. Acad. Sci. U.S.A. 101, 14859-14864.   DOI
67 Sugie, K., Kawakami, T., Maeda, Y., Kawabe, T., Uchida, A. and Yodoi, J. (1991) Fyn tyrosine kinase associated with Fc epsilon RII/CD23: possible multiple roles in lymphocyte activation. Proc. Natl. Acad. Sci. U.S.A. 88, 9132-9135.   DOI
68 Zhang, C., Lu, X., Tan, Y., Li, B., Miao, X., Jin, L., Shi, X., Zhang, X., Miao, L., Li, X. and Cai, L. (2012) Diabetes-induced hepatic pathogenic damage, inflammation, oxidative stress, and insulin resistance was exacerbated in zinc deficient mouse model. PLoS ONE 7, e49257.   DOI
69 Yu, C. C., Yen, T. S., Lowell, C. A. and DeFranco, A. L. (2001) Lupuslike kidney disease in mice deficient in the Src family tyrosine kinases Lyn and Fyn. Curr. Biol. 11, 34-38.   DOI
70 Yu, L., Lin, Q., Liao, H., Feng, J., Dong, X. and Ye, J. (2010) TGFbeta1 induces podocyte injury through Smad3-ERK-NF-kappaB pathway and Fyn-dependent TRPC6 phosphorylation. Cell Physiol. Biochem. 26, 869-878.   DOI
71 Zhao, L., Zhang, C., Luo, X., Wang, P., Zhou, W., Zhong, S., Xie, Y., Jiang, Y., Yang, P., Tang, R., Pan, Q., Hall, A. R., Luong, T. V., Fan, J., Varghese, Z., Moorhead, J. F., Pinzani, M., Chen, Y. and Ruan, X. Z. (2018) CD36 palmitoylation disrupts free fatty acid metabolism and promotes tissue inflammation in non-alcoholic steatohepatitis. J. Hepatol. 69, 705-717.   DOI
72 Chen, J., Elfiky, A., Han, M., Chen, C. and Saif, M. W. (2014) The role of Src in colon cancer and its therapeutic implications. Clin. Colorectal Cancer 13, 5-13.   DOI
73 Zheng, M., Zhang, Q., Joe, Y., Kim, S. K., Uddin, M. J., Rhew, H., Kim, T., Ryter, S. W. and Chung, H. T. (2013) Carbon monoxide-releasing molecules reverse leptin resistance induced by endoplasmic reticulum stress. Am. J. Physiol. Endocrinol. Metab. 304, 780-788.
74 Bonventre, J. V. and Zuk, A. (2004) Ischemic acute renal failure: an inflammatory disease? Kidney Int. 66, 480-485.   DOI
75 Calautti, E., Grossi, M., Mammucari, C., Aoyama, Y., Pirro, M., Ono, Y., Li, J. and Dotto, G. P. (2002) Fyn tyrosine kinase is a downstream mediator of Rho/PRK2 function in keratinocyte cell-cell adhesion. J. Cell Biol. 156, 137-148.   DOI
76 Calfon, M., Zeng, H., Urano, F., Till, J. H., Hubbard, S. R., Harding, H. P., Clark, S. G. and Ron, D. (2002) IRE1 couples endoplasmic reticulum load to secretory capacity by processing the XBP-1 mRNA. Nature 415, 92-96.   DOI
77 Chen, H. and Busse, L. W. (2017) Novel therapies for acute kidney injury. Kidney Int. Rep. 2, 785-799.   DOI
78 Cooke, M. P. and Perlmutter, R. M. (1989) Expression of a novel form of the fyn proto-oncogene in hematopoietic cells. New Biol. 1, 66-74.
79 Cheng, Y., Zhang, J., Guo, W., Li, F., Sun, W., Chen, J., Zhang, C., Lu, X., Tan, Y., Feng, W., Fu, Y., Liu, G. C., Xu, Z. and Cai, L. (2016) Up-regulation of Nrf2 is involved in FGF21-mediated fenofibrate protection against type 1 diabetic nephropathy. Free Radic. Biol. Med. 93, 94-109.   DOI
80 Coca, S. G., Singanamala, S. and Parikh, C. R. (2012) Chronic kidney disease after acute kidney injury: a systematic review and metaanalysis. Kidney Int. 81, 442-448.   DOI
81 Benoit, S. W. and Devarajan, P. (2018) Acute kidney injury: emerging pharmacotherapies in current clinical trials. Pediatr. Nephrol. 33, 779-787.   DOI
82 Linkermann, A., Chen, G., Dong, G., Kunzendorf, U., Krautwald, S. and Dong, Z. (2014) Regulated cell death in AKI. J. Am. Soc. Nephrol. 25, 2689-2701.   DOI
83 Li, H., Lemay, S., Aoudjit, L., Kawachi, H. and Takano, T. (2004) SRCfamily kinase Fyn phosphorylates the cytoplasmic domain of nephrin and modulates its interaction with podocin. J. Am. Soc. Nephrol. 15, 3006-3015.   DOI
84 Li, X., Hassoun, H. T., Santora, R. and Rabb, H. (2009) Organ crosstalk: the role of the kidney. Curr. Opin. Crit. Care 15, 481-487.   DOI
85 Li, W., Febbraio, M., Reddy, S. P., Yu, D. Y., Yamamoto, M. and Silverstein, R. L. (2010) CD36 participates in a signaling pathway that regulates ROS formation in murine VSMCs. J. Clin. Invest. 120, 3996-4006.   DOI
86 Liu, D., Zhang, X., Hu, B. and Ander, B. P. (2016) Src family kinases in brain edema after acute brain injury. Acta Neurochir. Suppl. 121, 185-190.   DOI
87 Lv, Z., Hu, M., Ren, X., Fan, M., Zhen, J., Chen, L., Lin, J., Ding, N., Wang, Q. and Wang, R. (2016) Fyn mediates high glucose-induced actin cytoskeleton reorganization of podocytes via promoting ROCK activation in vitro. J. Diabetes Res. 2016, 5671803.
88 Matsushita, K., Saritas, T., Eiwaz, M. B., McClellan, N., Coe, I., Zhu, W., Ferdaus, M. Z., Sakai, L. Y., McCormick, J. A. and Hutchens, M. P. (2019) The acute kidney injury to chronic kidney disease transition in a mouse model of acute cardiorenal syndrome emphasizes the role of inflammation. Kidney Int. 19, 30774-30784.
89 Mittwede, P. N., Xiang, L., Lu, S., Clemmer, J. S. and Hester, R. L. (2015) Oxidative stress contributes to orthopedic trauma-induced acute kidney injury in obese rats. Am. J. Physiol. Renal Physiol. 308, 157-163.
90 McCaffrey, J., Dhakal, A. K., Milford, D. V., Webb, N. J. and Lennon, R. (2017) Recent developments in the detection and management of acute kidney injury. Arch. Dis. Child. 102, 91-96.   DOI
91 Urano, F., Wang, X., Bertolotti, A., Zhang, Y., Chung, P., Harding, H. P. and Ron, D. (2000) Coupling of stress in the ER to activation of JNK protein kinases by transmembrane protein kinase IRE1. Science 287, 664-666.   DOI
92 Suzuki, C., Isaka, Y., Takabatake, Y., Tanaka, H., Koike, M., Shibata, M., Uchiyama, Y., Takahara, S. and Imai, E. (2008) Participation of autophagy in renal ischemia/reperfusion injury. Biochem. Biophys. Res. Commun. 368, 100-106.   DOI
93 Taniguchi, K., Xia, L., Goldberg, H. J., Lee, K. W., Shah, A., Stavar, L., Masson, E. A., Momen, A., Shikatani, E. A., John, R., Husain, M. and Fantus, I. G. (2013) Inhibition of Src kinase blocks high glucose-induced EGFR transactivation and collagen synthesis in mesangial cells and prevents diabetic nephropathy in mice. Diabetes 62, 3874-3886.   DOI
94 Uddin, M. J., Pak, E. S. and Ha, H. (2018) Carbon monoxide releasing molecule-2 protects mice against acute kidney injury through inhibition of ER stress. Korean J. Physiol. Pharmacol. 22, 567-575.   DOI
95 Verma, R., Wharram, B., Kovari, I., Kunkel, R., Nihalani, D., Wary, K. K., Wiggins, R. C., Killen, P. and Holzman, L. B. (2003) Fyn binds to and phosphorylates the kidney slit diaphragm component Nephrin. J. Biol. Chem. 278, 20716-20723.   DOI
96 Wang, Y., Yamada, E., Zong, H. and Pessin, J. E. (2015) Fyn activation of mTORC1 stimulates the IRE1alpha-JNK pathway, leading to cell death. J. Biol. Chem. 290, 24772-24783.   DOI