Diabetic Nephropathy. In 2014 (according to data published by the World Health Organization) 9% of the global population was affected by Diabetes which was considered to be directly responsible for 1.5 million deaths just two years prior (in 2012). From the entire number of patients suffering from diabetes, approximately a quarter of them develop renal affection. Diabetic nephropathy has similar physiopathology mechanisms and ultrastructural changes in cell injury characteristics in both Type 1 and Type 2 diabetes.
Cell Death. Cell Death was less studied in the renal diabetic disease, although it could represent an important pathogenic mechanism in the appearance and progression of nephropathy. At renal level the cellular loss can be explained by several mechanisms; different stimuli with cellular lesion potential can trigger apoptosis signaling with appearance of regulatory proteins having a double role (they participate in the initiation of the apoptosis path and cell death or in the ending of this process). The types of Cell Death and their relative proportion between themselves in the renal tissue have not been completely elucidated.
Caspases. Discovered in the middle of the 1990’s, Caspases are a part of the cysteine proteases family and play a role in numerous aspects of physiology (having a role in development, aging and apoptosis), but also in aspects of physiopathology of several degenerative affections, autoimmune diseases, oncologic diseases – having an important part in apoptosis, necrosis and also inflammation.
3. WHO. Global status report on noncommunicable diseases 2010. World Health Organization. 2011.
4. R. ALPERN, M. CAPLAN, O. MOE. Seldin and Giebisch's The Kidney; Physiology & Pathophysiology. Academic Press; 2012. p. 2605-23.
5. ALNEMRI ES, LIVINGSTON DJ, NICHOLSON DW, SALVESEN G, THORNBERRY NA, WONG WW, et al. Human ICE/CED-3 protease nomenclature. Cell. 1996; 87(2): 171.
6. FIORETTO P, STEFFES MW, BROWN DM, MAUER SM. An overview of renal pathology in insulin-dependent diabetes mellitus in relationship to altered glomerular hemodynamics. Am J Kidney Dis. 1992; 20(6): 549-58.
7. COVIC A., COVIC M., SEGALL L., GUSBETH-TATOMIR P. Manual de Nefrologie. Polirom; 2007.
8. GOLDIN A, BECKMAN JA, SCHMIDT AM, CREAGER MA. Advanced glycation end products: sparking the development of diabetic vascular injury. Circulation. 2006; 114(6): 597-605.
9. ZHANG C, LIAO Y, Li Q, CHEN M, ZHAO Q, DENG R, et al. Recombinant adiponectin ameliorates liver ischemia reperfusion injury via activating the AMPK/eNOS pathway. PLoS One. 2013; 8(6): e66382.
10. FUJII Y, OKADA A, YASUI T, NIIMI K, HAMAMOTO S, HIROSE M, et al. Effect of adiponectin on kidney crystal formation in metabolic syndrome model mice via inhibition of inflammation and apoptosis. PLoS One. 2013; 8(4): e61343.
11. DING M, CARRAO AC, WAGNER RJ, XIE Y, JIN Y, RZUCIDLO EM, et al. Vascular smooth muscle cell-derived adiponectin: a paracrine regulator of contractile phenotype. J Mol Cell Cardiol. 2012; 52(2): 474-84.
12. QATANANI M, LAZAR MA. Mechanisms of obesity-associated insulin resistance: many choices on the menu. Genes Dev. 2007; 21(12): 1443-55.
13. WOLF G, ZIYADEH FN. Molecular mechanisms of diabetic renal hypertrophy. Kidney Int. 1999; 56(2): 393-405.
14. RIGALLEAU V, GARCIA M, LASSEUR C, LAURENT F, MONTAUDON M, RAFFAITIN C, et al. Large kidneys predict poor renal outcome in subjects with diabetes and chronic kidney disease. BMC Nephrol. 2010; 11: 3.
15. PENESCU M, MANDACHE E. The value of kidney biopsy in diabetes mellitus. Rom J Morphol Embryol. 2010; 51(1): 13-9.
16. DALLA VESTRA M, SALLER A, MAUER M, FIORETTO P. Role of mesangial expansion in the pathogenesis of diabetic nephropathy. J Nephrol. 2001; 14 Suppl 4: S51-7.
17. SUSZTAK K, RAFF AC, SCHIFFER M, BOTTINGER EP. Glucose-induced reactive oxygen species cause apoptosis of podocytes and podocyte depletion at the onset of diabetic nephropathy. Diabetes. 2006; 55(1): 225-33.
18. ZHANG Y, SHI Y, LIU Y, DONG H, LIU M, LI Y, et al. Growth pattern switch of renal cells and expression of cell cycle related proteins at the early stage of diabetic nephropathy. Biochem Biophys Res Commun. 2007; 363(1): 159-64.
19. WOLF G. Cell cycle regulation in diabetic nephropathy. Kidney Int Suppl. 2000; 77: S59-66.
20. HARPER JW, ADAMI GR, WEI N, KEYOMARSI K, ELLEDGE SJ. The p21 Cdk-interacting protein Cip1 is a potent inhibitor of G1 cyclin-dependent kinases. Cell. 1993; 75(4): 805-16.
21. ALMOND JB, COHEN GM. The proteasome: a novel target for cancer chemotherapy. Leukemia. 2002; 16(4): 433-43.
22. GERVAIS JL, SETH P, ZHANG H. Cleavage of CDK inhibitor p21(Cip1/Waf1) by caspases is an early event during DNA damage-induced apoptosis. J Biol Chem. 1998; 273(30): 19207-12.
23. WOLF G, SCHROEDER R, ZIYADEH FN, THAISS F, ZAHNER G, STAHL RA. High glucose stimulates expression of p27Kip1 in cultured mouse mesangial cells: relationship to hypertrophy. Am J Physiol. 1997; 273(3 Pt 2): F348-56.
24. RANE MJ, SONG Y, JIN S, BARATI MT, WU R, KAUSAR H, et al. Interplay between Akt and p38 MAPK pathways in the regulation of renal tubular cell apoptosis associated with diabetic nephropathy. Am J Physiol Renal Physiol. 2010; 298(1): F49-61.
25. ELMORE S. Apoptosis: a review of programmed cell death. Toxicol Pathol. 2007; 35(4): 495-516.
26. ALBERTS B JA, LEWIS J, et al., editor. Molecular Biology of the Cell. 4th edition ed. New York: Garland Science; 2002.
27. KUMAR D, ROBERTSON S, BURNS KD. Evidence of apoptosis in human diabetic kidney. Mol Cell Biochem. 2004; 259(1-2): 67-70.
28. HOTCHKISS RS, STRASSER A, McDUNN JE, SWANSON PE. Cell death. N Engl J Med. 2009; 361(16): 1570-83.
29. URSEA N, editor. Esentialul in Nefrologie: Fundaţia Română a Rinichiului; 2002.
31. CABON L, MARTINEZ-TORRES AC, SUSIN SA. Programmed cell death comes in many flavors. Med Sci (Paris). 2013; 29 (12): 1117-24.
32. McLUSKEY K, MOTTRAM JC. Comparative structural analysis of the caspase family with other clan CD cysteine peptidases. Biochem J. 2015; 466(2): 219-32.
33. TOWNS R, PIETROPAOLO M, WILEY JW. Stimulation of autophagy by autoantibody-mediated activation of death receptor cascades. Autophagy. 2008; 4(5): 715-6.
34. ACEHAN D, JIANG X, MORGAN DG, HEUSER JE, WANG X, AKEY CW. Three-dimensional structure of the apoptosome: implications for assembly, procaspase-9 binding, and activation. Mol Cell. 2002; 9(2): 423-32.
35. DOLEZALOVA D, MRAZ M, BARTA T, PLEVOVA K, VINARSKY V, HOLUBCOVA Z, et al. MicroRNAs regulate p21(Waf1/Cip1) protein expression and the DNA damage response in human embryonic stem cells. Stem Cells. 2012; 30(7): 1362-72.
36. LEE HB, YU MR, YANG Y, JIANG Z, HA H. Reactive oxygen species-regulated signaling pathways in diabetic nephropathy. J Am Soc Nephrol. 2003; 14(8 Suppl 3): S241-5.