Polycystic kidneys: interaction of notch and renin.

Polycystic kidney disease (PKD) is a developmental disorder, which either manifests in early childhood or later in life, depending on the genetic mutation one harbors. The mechanisms of cyst initiation are not well understood. Increasing literature is now suggesting that Notch signaling may play a critical role in PKD. Activation of Notch signaling is important during nephrogenesis and slows down after development. Deletion of various Notch molecules in the cap mesenchyme leads to formation of cysts and early death in mice. A new study by Belyea et al. has now found that cells of renin lineage may link Notch expression and cystic kidney disease. Here, we use our understanding of Notch signaling and PKD to speculate about the significance of these interactions.

[1]  A. Fogo,et al.  Overexpression of notch signaling in renin cells leads to a polycystic kidney phenotype. , 2022, Clinical science.

[2]  P. Boor,et al.  Activation of Notch3 in Renal Tubular Cells Leads to Progressive Cystic Kidney Disease , 2022, International journal of molecular sciences.

[3]  L. Navar,et al.  The evolving complexity of the collecting duct renin–angiotensin system in hypertension , 2021, Nature Reviews Nephrology.

[4]  L. Díaz-Rodríguez,et al.  Hajdu–Cheney Syndrome: A Systematic Review of the Literature , 2020, International journal of environmental research and public health.

[5]  C. Ward,et al.  Notch4 activation aggravates NF-κB-mediated inflammation in HIV-1-associated nephropathy , 2019, Disease Models & Mechanisms.

[6]  B. Magenheimer,et al.  Aberrant Regulation of Notch3 Signaling Pathway in Polycystic Kidney Disease , 2018, Scientific Reports.

[7]  R. A. Gomez,et al.  Fate of Renin Cells During Development and Disease , 2017, Hypertension.

[8]  A. Cohen-Solal,et al.  Loss of Notch3 Signaling in Vascular Smooth Muscle Cells Promotes Severe Heart Failure Upon Hypertension , 2016, Hypertension.

[9]  M. L. Sequeira-Lopez,et al.  Loss of Jagged1 in renin progenitors leads to focal kidney fibrosis , 2015, Physiological reports.

[10]  C. Chatziantoniou,et al.  Activation of Notch3 in Glomeruli Promotes the Development of Rapidly Progressive Renal Disease. , 2015, Journal of the American Society of Nephrology : JASN.

[11]  U. Lendahl,et al.  Notch3 Is Necessary for Blood Vessel Integrity in the Central Nervous System , 2015, Arteriosclerosis, thrombosis, and vascular biology.

[12]  C. Sigmund,et al.  The earliest metanephric arteriolar progenitors and their role in kidney vascular development. , 2015, American journal of physiology. Regulatory, integrative and comparative physiology.

[13]  T. Coffman,et al.  Classical Renin-Angiotensin system in kidney physiology. , 2014, Comprehensive Physiology.

[14]  R. A. Gomez,et al.  Fate and plasticity of renin precursors in development and disease , 2014, Pediatric Nephrology.

[15]  N. Spinner,et al.  Renal involvement and the role of Notch signalling in Alagille syndrome , 2013, Nature Reviews Nephrology.

[16]  P. Boor,et al.  Notch‐3 receptor activation drives inflammation and fibrosis following tubulointerstitial kidney injury , 2012, The Journal of pathology.

[17]  L. Liaw,et al.  muscle cells , 2012 .

[18]  B. Aronow,et al.  Genes that confer the identity of the renin cell. , 2011, Journal of the American Society of Nephrology : JASN.

[19]  S. Glenn,et al.  Transcriptional regulator RBP-J regulates the number and plasticity of renin cells. , 2011, Physiological genomics.

[20]  M. Gessler,et al.  Epithelial Notch signaling regulates interstitial fibrosis development in the kidneys of mice and humans. , 2010, The Journal of clinical investigation.

[21]  G. Germino,et al.  Pkd1 and Pkd2 Are Required for Normal Placental Development , 2010, PloS one.

[22]  K. Suszták,et al.  Expression of Notch pathway proteins correlates with albuminuria, glomerulosclerosis, and renal function. , 2010, Kidney international.

[23]  K. Dell,et al.  The renin-angiotensin system and hypertension in autosomal recessive polycystic kidney disease , 2010, Pediatric Nephrology.

[24]  Raphael Kopan,et al.  Reduced Notch signaling leads to renal cysts and papillary microadenomas. , 2010, Journal of the American Society of Nephrology : JASN.

[25]  B. Siroky,et al.  Glomerulocystic kidney disease , 2010, Pediatric Nephrology.

[26]  G. Chaturvedi,et al.  The homeodomain protein Cux1 interacts with Grg4 to repress p27 kip1 expression during kidney development. , 2009, Gene.

[27]  H. Kobori,et al.  Collecting Duct Renin: A major player in Angiotensin II-dependent Hypertension. , 2009, Journal of the American Society of Hypertension : JASH.

[28]  K. Suszták,et al.  The Notch pathway in podocytes plays a role in the development of glomerular disease , 2008, Nature Medicine.

[29]  M. DeRuiter,et al.  Pathogenic Sequence for Dissecting Aneurysm Formation in a Hypomorphic Polycystic Kidney Disease 1 Mouse Model , 2007, Arteriosclerosis, thrombosis, and vascular biology.

[30]  M. Iruela-Arispe,et al.  Notch signaling in blood vessels: who is talking to whom about what? , 2007, Circulation research.

[31]  M. Couillard,et al.  Overexpression of PKD1 Causes Polycystic Kidney Disease , 2006, Molecular and Cellular Biology.

[32]  S. Glenn,et al.  Activation of the Rat Renin Promoter by HOXD10·PBX1b·PREP1, Ets-1, and the Intracellular Domain of Notch* , 2005, Journal of Biological Chemistry.

[33]  T. Inagami,et al.  The intrarenal renin-angiotensin system in autosomal dominant polycystic kidney disease. , 2004, American journal of physiology. Renal physiology.

[34]  H. Kobori,et al.  Enhancement of Collecting Duct Renin in Angiotensin II–Dependent Hypertensive Rats , 2004, Hypertension.

[35]  O. Smithies,et al.  Renin cells are precursors for multiple cell types that switch to the renin phenotype when homeostasis is threatened. , 2004, Developmental cell.

[36]  U. Lendahl,et al.  Characterization of Notch3‐deficient mice: Normal embryonic development and absence of genetic interactions with a Notch1 mutation , 2003, Genesis.

[37]  J. Aster,et al.  An Invitation to T and More Notch Signaling in Lymphopoiesis , 2002, Cell.

[38]  Raphael Kopan,et al.  Notch signaling: from the outside in. , 2000, Developmental biology.

[39]  J. Sundberg,et al.  Notch signaling is essential for vascular morphogenesis in mice. , 2000, Genes & development.

[40]  K. Klinger,et al.  Polycystin 1 is required for the structural integrity of blood vessels. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[41]  S. Artavanis-Tsakonas,et al.  Notch Signaling : Cell Fate Control and Signal Integration in Development , 1999 .

[42]  P. Ratcliffe,et al.  Polycystin, the polycystic kidney disease 1 protein, is expressed by epithelial cells in fetal, adult, and polycystic kidney. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[43]  K. Gross,et al.  Recombination signal binding protein for Ig-κJ region regulates juxtaglomerular cell phenotype by activating the myo-endocrine program and suppressing ectopic gene expression. , 2015, Journal of the American Society of Nephrology : JASN.

[44]  M. Halushka,et al.  A Pkd1-Fbn1 genetic interaction implicates TGF-β signaling in the pathogenesis of vascular complications in autosomal dominant polycystic kidney disease. , 2014, Journal of the American Society of Nephrology : JASN.

[45]  S. Glenn,et al.  Control of rene gene expression , 2012, Pflügers Archiv - European Journal of Physiology.

[46]  Lin Geng,et al.  Cardiac defects and renal failure in mice with targeted mutations in Pkd2 , 2000, Nature Genetics.