The Korean journal of internal medicine

The Korean Association of Internal Medicine (대한내과학회)
권호 표지
DOI QR코드

DOI QR Code

Notch signaling in the collecting duct regulates renal tubulointerstitial fibrosis induced by unilateral ureteral obstruction in mice

  • Choi, Arum (Department of Anatomy and Cell Death Disease Research Center, College of Medicine, The Catholic University of Korea) ;
  • Nam, Sun Ah (Department of Anatomy and Cell Death Disease Research Center, College of Medicine, The Catholic University of Korea) ;
  • Kim, Wan-Young (Department of Anatomy and Cell Death Disease Research Center, College of Medicine, The Catholic University of Korea) ;
  • Park, Sang Hee (Institute of Clinical Medicine Research of Bucheon St. Mary's Hospital) ;
  • Kim, Hyang (Division of Nephrology, Department of Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine) ;
  • Yang, Chul Woo (Department of Internal Medicine, College of Medicine, The Catholic University of Korea) ;
  • Kim, Jin (Department of Anatomy and Cell Death Disease Research Center, College of Medicine, The Catholic University of Korea) ;
  • Kim, Yong Kyun (Department of Anatomy and Cell Death Disease Research Center, College of Medicine, The Catholic University of Korea)
  • Received : 2016.07.15
  • Accepted : 2016.09.24
  • Published : 2018.07.01
⟨ Previous Next ⟩

Abstract

Background/Aims: Mind bomb-1 (Mib1) encodes an E3 ubiquitin ligase, which is required for the initiation of Notch signaling. Recently, it was demonstrated that the renal collecting duct plays an important role in renal fibrosis. Here, we investigated the role of Notch signaling in renal fibrosis using conditional knockout mice with the specific ablation of Mib1 in renal collecting duct principal cells. Methods: Mib1-floxed mice ($Mib1^{f/f}$) were crossed with aquaporin 2 (AQP2)-Cre mice in order to generate principal cell-specific Mib1 knockout mice ($Mib1^{f/f}$:AQP2-$Cre^+$). Unilateral ureteral obstruction (UUO) was performed, and mice were sacrificed 7 days after UUO. Results: After performing the UUO, renal tubulointerstitial fibrosis and the expression of transforming growth factor ${\beta}$ were markedly enhanced in the obstructed kidneys of $Mib1^{f/f}$ mice compared with the sham-operated kidney of $Mib1^{f/f}$ mice. These changes were shown to be even more pronounced in the obstructed kidneys of $Mib1^{f/f}$ :AQP2-$Cre^+$ mice than in those of the $Mib1^{f/f}$ mice. Furthermore, the number of TUNNEL-positive cells in renal collecting duct was higher in the obstructed kidneys of $Mib1^{f/f}$ :AQP2-$Cre^+$ mice than in the kidneys of $Mib1^{f/f}$ mice. Conclusions: Notch signaling in the renal collecting duct plays an important role in the regulation of renal tubulointerstitial fibrosis and apoptosis after UUO.

Keywords

Acknowledgement

Supported by : National Research Foundation of Korea (NRF), MRC, institute of Clinical Medicine Research of Bucheon St. Mary's Hospital

References

  1. Kriz W, Elger M, Hosser H, et al. How does podocyte damage result in tubular damage? Kidney Blood Press Res 1999;22:26-36. https://doi.org/10.1159/000025906
  2. Sutariya B, Jhonsa D, Saraf MN. TGF-${\beta}$: the connecting link between nephropathy and fibrosis. Immunopharmacol Immunotoxicol 2016;38:39-49. https://doi.org/10.3109/08923973.2015.1127382
  3. Yan J, Zhang Z, Jia L, Wang Y. Role of bone marrow-derived fibroblasts in renal fibrosis. Front Physiol 2016;7:61.
  4. Nath KA. Tubulointerstitial changes as a major determinant in the progression of renal damage. Am J Kidney Dis 1992;20:1-17. https://doi.org/10.1016/S0272-6386(12)80312-X
  5. Eddy AA. The origin of scar-forming kidney myofibroblasts. Nat Med 2013;19:964-966. https://doi.org/10.1038/nm.3299
  6. Kopan R, Ilagan MX. The canonical Notch signaling pathway: unfolding the activation mechanism. Cell 2009;137:216-233. https://doi.org/10.1016/j.cell.2009.03.045
  7. Le Borgne R. Regulation of Notch signalling by endocytosis and endosomal sorting. Curr Opin Cell Biol 2006;18:213-222. https://doi.org/10.1016/j.ceb.2006.02.011
  8. Boulianne GL, de la Concha A, Campos-Ortega JA, Jan LY, Jan YN. The Drosophila neurogenic gene neuralized encodes a novel protein and is expressed in precursors of larval and adult neurons. EMBO J 1993;12:2586.
  9. Itoh M, Kim CH, Palardy G, et al. Mind bomb is a ubiquitin ligase that is essential for efficient activation of Notch signaling by delta. Dev Cell 2003;4:67-82. https://doi.org/10.1016/S1534-5807(02)00409-4
  10. Koo BK, Yoon MJ, Yoon KJ, et al. An obligatory role of mind bomb-1 in notch signaling of mammalian development. PLoS One 2007;2:e1221. https://doi.org/10.1371/journal.pone.0001221
  11. Jeong HW, Jeon US, Koo BK, et al. Inactivation of Notch signaling in the renal collecting duct causes nephrogenic diabetes insipidus in mice. J Clin Invest 2009;119:3290-3300.
  12. Niranjan T, Bielesz B, Gruenwald A, et al. The Notch pathway in podocytes plays a role in the development of glomerular disease. Nat Med 2008;14:290-298. https://doi.org/10.1038/nm1731
  13. Bielesz B, Sirin Y, Si H, et al. Epithelial Notch signaling regulates interstitial fibrosis development in the kidneys of mice and humans. J Clin Invest 2010;120:4040-4054. https://doi.org/10.1172/JCI43025
  14. Butt MJ, Tarantal AF, Jimenez DF, Matsell DG. Collecting duct epithelial-mesenchymal transition in fetal urinary tract obstruction. Kidney Int 2007;72:936-944. https://doi.org/10.1038/sj.ki.5002457
  15. Ivanova L, Butt MJ, Matsell DG. Mesenchymal transition in kidney collecting duct epithelial cells. Am J Physiol Renal Physiol 2008;294:F1238-F1248. https://doi.org/10.1152/ajprenal.00326.2007
  16. Smith JP, Pozzi A, Dhawan P, Singh AB, Harris RC. Soluble HB-EGF induces epithelial-to-mesenchymal transition in inner medullary collecting duct cells by upregulating Snail-2. Am J Physiol Renal Physiol 2009;296:F957-F965. https://doi.org/10.1152/ajprenal.90490.2008
  17. Fujiu K, Manabe I, Nagai R. Renal collecting duct epithelial cells regulate inflammation in tubulointerstitial damage in mice. J Clin Invest 2011;121:3425-3441. https://doi.org/10.1172/JCI57582
  18. Ding Y, Kim SI, Lee SY, Koo JK, Wang Z, Choi ME. Autophagy regulates TGF-${\beta}$ expression and suppresses kidney fibrosis induced by unilateral ureteral obstruction. J Am Soc Nephrol 2014;25:2835-2846. https://doi.org/10.1681/ASN.2013101068
  19. Hiatt MJ, Ivanova L, Trnka P, Solomon M, Matsell DG. Urinary tract obstruction in the mouse: the kinetics of distal nephron injury. Lab Invest 2013;93:1012-1023. https://doi.org/10.1038/labinvest.2013.90
  20. Kobayashi T, Terada Y, Kuwana H, et al. Expression and function of the delta-1/Notch-2/Hes-1 pathway during experimental acute kidney injury. Kidney Int 2008;73:1240-1250. https://doi.org/10.1038/ki.2008.74
  21. Pelengaris S, Khan M, Evan G. c-MYC: more than just a matter of life and death. Nat Rev Cancer 2002;2:764-776. https://doi.org/10.1038/nrc904
  22. Pelengaris S, Khan M. The many faces of c-MYC. Arch Biochem Biophys 2003;416:129-136. https://doi.org/10.1016/S0003-9861(03)00294-7
  23. Cianfanelli V, Fuoco C, Lorente M, et al. AMBRA1 links autophagy to cell proliferation and tumorigenesis by promoting c-Myc dephosphorylation and degradation. Nat Cell Biol 2015;17:20-30.
  24. Forbes MS, Thornhill BA, Minor JJ, Gordon KA, Galarreta CI, Chevalier RL. Fight-or-flight: murine unilateral ureteral obstruction causes extensive proximal tubular degeneration, collecting duct dilatation, and minimal fibrosis. Am J Physiol Renal Physiol 2012;303:F120-F129. https://doi.org/10.1152/ajprenal.00110.2012

Cited by

  1. The Significance of NOTCH Pathway in the Development of Fibrosis in Systemic Sclerosis vol.31, pp.4, 2018, https://doi.org/10.5021/ad.2019.31.4.365
  2. NOTCH3 T6746C and TP53 P72R Polymorphisms Are Associated with the Susceptibility to Diffuse Cutaneous Systemic Sclerosis vol.2020, pp.None, 2018, https://doi.org/10.1155/2020/8465971
  3. Collecting Duct-Specific CR6-Interacting Factor-1-Deletion Aggravates Renal Inflammation and Fibrosis Induced by Unilateral Ureteral Obstruction vol.22, pp.21, 2021, https://doi.org/10.3390/ijms222111699
  4. Stem cells in the treatment of renal fibrosis: a review of preclinical and clinical studies of renal fibrosis pathogenesis vol.12, pp.1, 2021, https://doi.org/10.1186/s13287-021-02391-w