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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)
  • Received : 2019.12.17
  • Accepted : 2020.04.06
  • Published : 2020.05.01

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

References

  1. Abram, C. L. and Lowell, C. A. (2008) The diverse functions of Src family kinases in macrophages. Front. Biosci. 13, 4426-4450. https://doi.org/10.2741/3015
  2. 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. https://doi.org/10.1128/MCB.06159-11
  3. 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. https://doi.org/10.3389/fphar.2019.01192
  4. 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. https://doi.org/10.1016/j.redox.2014.02.008
  5. 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. https://doi.org/10.1016/0092-8674(92)90309-z
  6. 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. https://doi.org/10.1681/ASN.2009050462
  7. 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. https://doi.org/10.1073/pnas.0506854103
  8. Basile, D. P., Anderson, M. D. and Sutton, T. A. (2012) Pathophysiology of acute kidney injury. Compr. Physiol. 2, 1303-1353. https://doi.org/10.1002/cphy.c110041
  9. 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. https://doi.org/10.1016/j.cmet.2007.04.005
  10. 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. https://doi.org/10.1186/cc2460
  11. Benoit, S. W. and Devarajan, P. (2018) Acute kidney injury: emerging pharmacotherapies in current clinical trials. Pediatr. Nephrol. 33, 779-787. https://doi.org/10.1007/s00467-017-3695-3
  12. Bonventre, J. V. and Zuk, A. (2004) Ischemic acute renal failure: an inflammatory disease? Kidney Int. 66, 480-485. https://doi.org/10.1111/j.1523-1755.2004.761_2.x
  13. 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. https://doi.org/10.1083/jcb.200105140
  14. 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. https://doi.org/10.1038/415092a
  15. Chen, H. and Busse, L. W. (2017) Novel therapies for acute kidney injury. Kidney Int. Rep. 2, 785-799. https://doi.org/10.1016/j.ekir.2017.06.020
  16. 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. https://doi.org/10.1016/j.clcc.2013.10.003
  17. 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. https://doi.org/10.1016/j.freeradbiomed.2016.02.002
  18. 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. https://doi.org/10.1038/ki.2011.379
  19. 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.
  20. 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. https://doi.org/10.1084/jem.175.6.1483
  21. 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. https://doi.org/10.1128/MCB.14.7.4554
  22. 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. https://doi.org/10.1186/scrt215
  23. 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. https://doi.org/10.1681/ASN.2016091001
  24. 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. https://doi.org/10.1080/13543784.2017.1274730
  25. 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. https://doi.org/10.1111/j.1742-7843.2011.00854.x
  26. 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. https://doi.org/10.1016/S0006-291X(02)02510-X
  27. 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. https://doi.org/10.1097/shk.0b013e318240b52a
  28. 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. https://doi.org/10.1016/j.yexcr.2012.03.011
  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. https://doi.org/10.1074/jbc.M611336200
  30. Jang, H. R. and Rabb, H. (2009) The innate immune response in ischemic acute kidney injury. Clin. Immunol. 130, 41-50. https://doi.org/10.1016/j.clim.2008.08.016
  31. 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. https://doi.org/10.1021/jm0607202
  32. 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. https://doi.org/10.2353/ajpath.2010.090594
  33. 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. https://doi.org/10.1038/cdd.2011.98
  34. 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. https://doi.org/10.1111/j.1939-1676.2010.0498.x
  35. 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. https://doi.org/10.1038/ncb2152
  36. 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. https://doi.org/10.4049/jimmunol.1401399
  37. 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. https://doi.org/10.1124/mol.111.077149
  38. Kroemer, G., Marino, G. and Levine, B. (2010) Autophagy and the integrated stress response. Mol. Cell 40, 280-293. https://doi.org/10.1016/j.molcel.2010.09.023
  39. 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. https://doi.org/10.1073/pnas.95.11.6448
  40. 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. https://doi.org/10.1016/j.tvjl.2014.10.009
  41. 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. https://doi.org/10.2337/db12-0920
  42. 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. https://doi.org/10.1038/ki.2013.153
  43. 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.
  44. 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. https://doi.org/10.1097/01.ASN.0000146689.88078.80
  45. 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. https://doi.org/10.1097/MCC.0b013e328332f69e
  46. 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. https://doi.org/10.1172/JCI42823
  47. 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. https://doi.org/10.1681/asn.2014030262
  48. 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. https://doi.org/10.1007/978-3-319-18497-5_33
  49. 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.
  50. 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.
  51. 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. https://doi.org/10.1136/archdischild-2015-309381
  52. 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.
  53. 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. https://doi.org/10.1038/ki.2013.74
  54. 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. https://doi.org/10.1038/s41467-017-00294-0
  55. 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. https://doi.org/10.1073/pnas.87.21.8622
  56. 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. https://doi.org/10.1016/j.ejphar.2019.172711
  57. 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. https://doi.org/10.1038/s41467-018-06844-4
  58. 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. https://doi.org/10.1038/ncomms5425
  59. 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. https://doi.org/10.1523/JNEUROSCI.0302-15.2015
  60. 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. https://doi.org/10.14740/jocmr3852
  61. 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. https://doi.org/10.1038/ni.2708
  62. 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. https://doi.org/10.1023/a:1009680229931
  63. Resh, M. D. (1998) Fyn, a Src family tyrosine kinase. Int. J. Biochem. Cell Biol. 30, 1159-1162. https://doi.org/10.1016/S1357-2725(98)00089-2
  64. Rifkin, D. E., Coca, S. G. and Kalantar-Zadeh, K. (2012) Does AKI truly lead to CKD? J. Am. Soc. Nephrol. 23, 979-984. https://doi.org/10.1681/ASN.2011121185
  65. 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. https://doi.org/10.1038/cddis.2014.118
  66. Roskoski, R., Jr. (2015) Src protein-tyrosine kinase structure, mechanism, and small molecule inhibitors. Pharmacol. Res. 94, 9-25. https://doi.org/10.1016/j.phrs.2015.01.003
  67. Saito, Y. D., Jensen, A. R., Salgia, R. and Posadas, E. M. (2010) Fyn: a novel molecular target in cancer. Cancer 116, 1629-1637. https://doi.org/10.1002/cncr.24879
  68. 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. https://doi.org/10.1016/j.neuro.2011.06.009
  69. 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.
  70. 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. https://doi.org/10.1038/srep12292
  71. 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. https://doi.org/10.2174/092986711796150531
  72. 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. https://doi.org/10.1016/j.molcel.2010.09.026
  73. 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. https://doi.org/10.1016/j.kint.2016.06.038
  74. 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. https://doi.org/10.1016/j.jnutbio.2014.12.008
  75. 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. https://doi.org/10.1073/pnas.0406168101
  76. 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. https://doi.org/10.1073/pnas.88.20.9132
  77. 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. https://doi.org/10.1016/j.bbrc.2008.01.059
  78. 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. https://doi.org/10.2337/db12-1010
  79. 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. https://doi.org/10.4196/kjpp.2018.22.5.567
  80. 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. https://doi.org/10.1126/science.287.5453.664
  81. 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. https://doi.org/10.1074/jbc.M301689200
  82. 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. https://doi.org/10.1074/jbc.M115.687020
  83. 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. https://doi.org/10.1016/j.mce.2015.09.008
  84. 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. https://doi.org/10.18632/oncotarget.16114
  85. 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. https://doi.org/10.3109/0886022X.2016.1160724
  86. 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. https://doi.org/10.1016/j.celrep.2012.03.014
  87. 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. https://doi.org/10.18632/oncotarget.11916
  88. 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. https://doi.org/10.1016/j.cmet.2009.12.010
  89. 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. https://doi.org/10.1038/ki.2015.293
  90. 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. https://doi.org/10.1152/ajprenal.00590.2007
  91. 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. https://doi.org/10.1159/000329385
  92. 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. https://doi.org/10.1016/S0960-9822(00)00024-5
  93. 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. https://doi.org/10.1159/000323996
  94. 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. https://doi.org/10.1371/journal.pone.0049257
  95. 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. https://doi.org/10.1016/j.jhep.2018.04.006
  96. 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.

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