{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nThe extensive body of literature provided here examines the molecular and cellular mechanisms underlying polycystic kidney disease. These studies detail how proteins such as polycystin‐1 and polycystin‐2 localize to primary cilia, engage in proteolytic processing and trafficking, and regulate diverse signaling pathways—including JAK‐STAT, mTOR, Wnt, and calcium‐dependent cascades—that control cell proliferation, differentiation, and tissue morphogenesis in renal and extra‐renal tissues."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "10"}]}, {"type": "t", "text": " These works collectively emphasize the importance of coordinated ciliary function and protein complex assembly in maintaining normal renal architecture and in the pathogenesis of cyst formation."}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIt is important to note, however, that none of these abstracts provide any experimental evidence or discussion regarding TTC38. Although TTC38 (likely referring to a protein harboring tetratricopeptide repeat motifs that in other contexts can mediate protein–protein interactions) might be hypothesized to influence aspects of complex assembly or signaling regulation, its function is not addressed in the literature cited here. In other words, while the studies offer rich insights into the regulatory networks of polycystins and associated pathways in polycystic kidney disease"}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "11", "end_ref": "39"}]}, {"type": "t", "text": ", they offer no data from which to infer a role for TTC38. Future studies will be needed to clarify whether TTC38 participates directly or indirectly in these complex cellular networks."}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "W Lu, X Shen, A Pavlova, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "Polycystin-1 activation of c-Jun N-terminal kinase and AP-1 is mediated by heterotrimeric G proteins."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M201875200"}], "href": "https://doi.org/10.1074/jbc.M201875200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "11912216"}], "href": "https://pubmed.ncbi.nlm.nih.gov/11912216"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Anil Kumar Bhunia, Klaus Piontek, Alessandra Boletta, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "Functional analysis of PKD1 transgenic lines reveals a direct role for polycystin-1 in mediating cell-cell adhesion."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Am Soc Nephrol (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1097/01.asn.0000076075.49819.9b"}], "href": "https://doi.org/10.1097/01.asn.0000076075.49819.9b"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12819240"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12819240"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "David H Grimm, Yiqiang Cai, Veronique Chauvet, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Polycystin-1 distribution is modulated by polycystin-2 expression in mammalian cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M306536200"}], "href": "https://doi.org/10.1074/jbc.M306536200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12840011"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12840011"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Veronique Chauvet, Xin Tian, Herve Husson, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Mechanical stimuli induce cleavage and nuclear translocation of the polycystin-1 C terminus."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Clin Invest (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1172/JCI21753"}], "href": "https://doi.org/10.1172/JCI21753"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15545994"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15545994"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Saori Nishio, Masahiko Hatano, Michio Nagata, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Pkd1 regulates immortalized proliferation of renal tubular epithelial cells through p53 induction and JNK activation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Clin Invest (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1172/JCI22850"}], "href": "https://doi.org/10.1172/JCI22850"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15761494"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15761494"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Caroline Thivierge, Almira Kurbegovic, Martin Couillard, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Overexpression of PKD1 causes polycystic kidney disease."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell Biol (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1128/MCB.26.4.1538-1548.2006"}], "href": "https://doi.org/10.1128/MCB.26.4.1538-1548.2006"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16449663"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16449663"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Zhousheng Xiao, Shiqin Zhang, Josh Mahlios, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Cilia-like structures and polycystin-1 in osteoblasts/osteocytes and associated abnormalities in skeletogenesis and Runx2 expression."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M604772200"}], "href": "https://doi.org/10.1074/jbc.M604772200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16905538"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16905538"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Ali K Ahrabi, Sara Terryn, Giovanna Valenti, et al. "}, {"type": "b", "children": [{"type": "t", "text": "PKD1 haploinsufficiency causes a syndrome of inappropriate antidiuresis in mice."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Am Soc Nephrol (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1681/ASN.2006010052"}], "href": "https://doi.org/10.1681/ASN.2006010052"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17475819"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17475819"}]}, {"type": "r", "ref": 12, "children": [{"type": "t", "text": "Sabrine Hassane, Nanna Claij, Irma S Lantinga-van Leeuwen, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Pathogenic sequence for dissecting aneurysm formation in a hypomorphic polycystic kidney disease 1 mouse model."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Arterioscler Thromb Vasc Biol (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1161/ATVBAHA.107.149252"}], "href": "https://doi.org/10.1161/ATVBAHA.107.149252"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17656674"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17656674"}]}, {"type": "r", "ref": 13, "children": [{"type": "t", "text": "Irma S Lantinga-van Leeuwen, Wouter N Leonhard, Annemieke van der Wal, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Kidney-specific inactivation of the Pkd1 gene induces rapid cyst formation in developing kidneys and a slow onset of disease in adult mice."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Mol Genet (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/hmg/ddm299"}], "href": "https://doi.org/10.1093/hmg/ddm299"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17932118"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17932118"}]}, {"type": "r", "ref": 14, "children": [{"type": "t", "text": "Klaus Piontek, Luis F Menezes, Miguel A Garcia-Gonzalez, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A critical developmental switch defines the kinetics of kidney cyst formation after loss of Pkd1."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Med (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/nm1675"}], "href": "https://doi.org/10.1038/nm1675"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17965720"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17965720"}]}, {"type": "r", "ref": 15, "children": [{"type": "t", "text": "Shengqiang Yu, Karl Hackmann, Jiangang Gao, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Essential role of cleavage of Polycystin-1 at G protein-coupled receptor proteolytic site for kidney tubular structure."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.0708217104"}], "href": "https://doi.org/10.1073/pnas.0708217104"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18003909"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18003909"}]}, {"type": "r", "ref": 16, "children": [{"type": "t", "text": "Surya M Nauli, Yoshifumi Kawanabe, John J Kaminski, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Endothelial cilia are fluid shear sensors that regulate calcium signaling and nitric oxide production through polycystin-1."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Circulation (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1161/CIRCULATIONAHA.107.710111"}], "href": "https://doi.org/10.1161/CIRCULATIONAHA.107.710111"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18285569"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18285569"}]}, {"type": "r", "ref": 17, "children": [{"type": "t", "text": "Jens Fielitz, Mi-Sung Kim, John M Shelton, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Requirement of protein kinase D1 for pathological cardiac remodeling."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.0712265105"}], "href": "https://doi.org/10.1073/pnas.0712265105"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18287012"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18287012"}]}, {"type": "r", "ref": 18, "children": [{"type": "t", "text": "Lorenzo Battini, Salvador Macip, Elena Fedorova, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Loss of polycystin-1 causes centrosome amplification and genomic instability."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Mol Genet (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/hmg/ddn180"}], "href": "https://doi.org/10.1093/hmg/ddn180"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18566106"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18566106"}]}, {"type": "r", "ref": 19, "children": [{"type": "t", "text": "Tiffiney R Hartman, Dongyan Liu, Jack T Zilfou, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The tuberous sclerosis proteins regulate formation of the primary cilium via a rapamycin-insensitive and polycystin 1-independent pathway."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Mol Genet (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/hmg/ddn325"}], "href": "https://doi.org/10.1093/hmg/ddn325"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18845692"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18845692"}]}, {"type": "r", "ref": 20, "children": [{"type": "t", "text": "Marie C Hogan, Luca Manganelli, John R Woollard, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Characterization of PKD protein-positive exosome-like vesicles."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Am Soc Nephrol (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1681/ASN.2008060564"}], "href": "https://doi.org/10.1681/ASN.2008060564"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19158352"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19158352"}]}, {"type": "r", "ref": 21, "children": [{"type": "t", "text": "Gianfranco Distefano, Manila Boca, Isaline Rowe, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Polycystin-1 regulates extracellular signal-regulated kinase-dependent phosphorylation of tuberin to control cell size through mTOR and its downstream effectors S6K and 4EBP1."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell Biol (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1128/MCB.01259-08"}], "href": "https://doi.org/10.1128/MCB.01259-08"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19255143"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19255143"}]}, {"type": "r", "ref": 22, "children": [{"type": "t", "text": "Hester Happé, Wouter N Leonhard, Annemieke van der Wal, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Toxic tubular injury in kidneys from Pkd1-deletion mice accelerates cystogenesis accompanied by dysregulated planar cell polarity and canonical Wnt signaling pathways."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Mol Genet (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/hmg/ddp190"}], "href": "https://doi.org/10.1093/hmg/ddp190"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19401297"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19401297"}]}, {"type": "r", "ref": 23, "children": [{"type": "t", "text": "Ana P Bastos, Klaus Piontek, Ana M Silva, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Pkd1 haploinsufficiency increases renal damage and induces microcyst formation following ischemia/reperfusion."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Am Soc Nephrol (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1681/ASN.2008040435"}], "href": "https://doi.org/10.1681/ASN.2008040435"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19833899"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19833899"}]}, {"type": "r", "ref": 24, "children": [{"type": "t", "text": "Reza Sharif-Naeini, Joost H A Folgering, Delphine Bichet, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Polycystin-1 and -2 dosage regulates pressure sensing."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.cell.2009.08.045"}], "href": "https://doi.org/10.1016/j.cell.2009.08.045"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19879844"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19879844"}]}, {"type": "r", "ref": 25, "children": [{"type": "t", "text": "Saori Nishio, Xin Tian, Anna Rachel Gallagher, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Loss of oriented cell division does not initiate cyst formation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Am Soc Nephrol (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1681/ASN.2009060603"}], "href": "https://doi.org/10.1681/ASN.2009060603"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19959710"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19959710"}]}, {"type": "r", "ref": 26, "children": [{"type": "t", "text": "Jonathan M Shillingford, Klaus B Piontek, Gregory G Germino, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Rapamycin ameliorates PKD resulting from conditional inactivation of Pkd1."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Am Soc Nephrol (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1681/ASN.2009040421"}], "href": "https://doi.org/10.1681/ASN.2009040421"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20075061"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20075061"}]}, {"type": "r", "ref": 27, "children": [{"type": "t", "text": "Sheng Xia, Xiaogang Li, Teri Johnson, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Polycystin-dependent fluid flow sensing targets histone deacetylase 5 to prevent the development of renal cysts."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Development (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1242/dev.049437"}], "href": "https://doi.org/10.1242/dev.049437"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20181743"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20181743"}]}, {"type": "r", "ref": 28, "children": [{"type": "t", "text": "Miguel A Garcia-Gonzalez, Patricia Outeda, Qin Zhou, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Pkd1 and Pkd2 are required for normal placental development."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS One (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pone.0012821"}], "href": "https://doi.org/10.1371/journal.pone.0012821"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20862291"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20862291"}]}, {"type": "r", "ref": 29, "children": [{"type": "t", "text": "Wouter N Leonhard, Annemieke van der Wal, Zlata Novalic, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Curcumin inhibits cystogenesis by simultaneous interference of multiple signaling pathways: in vivo evidence from a Pkd1-deletion model."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Physiol Renal Physiol (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1152/ajprenal.00419.2010"}], "href": "https://doi.org/10.1152/ajprenal.00419.2010"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21345977"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21345977"}]}, {"type": "r", "ref": 30, "children": [{"type": "t", "text": "Arne Ittner, Helena Block, Christoph A Reichel, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Regulation of PTEN activity by p38δ-PKD1 signaling in neutrophils confers inflammatory responses in the lung."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Exp Med (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1084/jem.20120677"}], "href": "https://doi.org/10.1084/jem.20120677"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23129748"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23129748"}]}, {"type": "r", "ref": 31, "children": [{"type": "t", "text": "Vishal Patel, Sachin Hajarnis, Darren Williams, et al. "}, {"type": "b", "children": [{"type": "t", "text": "MicroRNAs regulate renal tubule maturation through modulation of Pkd1."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Am Soc Nephrol (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1681/ASN.2012030321"}], "href": "https://doi.org/10.1681/ASN.2012030321"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23138483"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23138483"}]}, {"type": "r", "ref": 32, "children": [{"type": "t", "text": "Luis F Menezes, Fang Zhou, Andrew D Patterson, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Network analysis of a Pkd1-mouse model of autosomal dominant polycystic kidney disease identifies HNF4α as a disease modifier."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS Genet (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pgen.1003053"}], "href": "https://doi.org/10.1371/journal.pgen.1003053"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23209428"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23209428"}]}, {"type": "r", "ref": 33, "children": [{"type": "t", "text": "Baptiste Coxam, Amélie Sabine, Neil I Bower, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Pkd1 regulates lymphatic vascular morphogenesis during development."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Rep (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.celrep.2014.03.063"}], "href": "https://doi.org/10.1016/j.celrep.2014.03.063"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24767999"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24767999"}]}, {"type": "r", "ref": 34, "children": [{"type": "t", "text": "Yiqiang Cai, Sorin V Fedeles, Ke Dong, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Altered trafficking and stability of polycystins underlie polycystic kidney disease."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Clin Invest (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1172/JCI67273"}], "href": "https://doi.org/10.1172/JCI67273"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25365220"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25365220"}]}, {"type": "r", "ref": 35, "children": [{"type": "t", "text": "Hyunho Kim, Hangxue Xu, Qin Yao, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Ciliary membrane proteins traffic through the Golgi via a Rabep1/GGA1/Arl3-dependent mechanism."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Commun (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/ncomms6482"}], "href": "https://doi.org/10.1038/ncomms6482"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25405894"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25405894"}]}, {"type": "r", "ref": 36, "children": [{"type": "t", "text": "Vladimir G Gainullin, Katharina Hopp, Christopher J Ward, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Polycystin-1 maturation requires polycystin-2 in a dose-dependent manner."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Clin Invest (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1172/JCI76972"}], "href": "https://doi.org/10.1172/JCI76972"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25574838"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25574838"}]}, {"type": "r", "ref": 37, "children": [{"type": "t", "text": "Zully Pedrozo, Alfredo Criollo, Pavan K Battiprolu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Polycystin-1 Is a Cardiomyocyte Mechanosensor That Governs L-Type Ca2+ Channel Protein Stability."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Circulation (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1161/CIRCULATIONAHA.114.013537"}], "href": "https://doi.org/10.1161/CIRCULATIONAHA.114.013537"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25888683"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25888683"}]}, {"type": "r", "ref": 38, "children": [{"type": "t", "text": "Luis F Menezes, Cheng-Chao Lin, Fang Zhou, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Fatty Acid Oxidation is Impaired in An Orthologous Mouse Model of Autosomal Dominant Polycystic Kidney Disease."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "EBioMedicine (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.ebiom.2016.01.027"}], "href": "https://doi.org/10.1016/j.ebiom.2016.01.027"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27077126"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27077126"}]}, {"type": "r", "ref": 39, "children": [{"type": "t", "text": "Ping Zhu, Cynthia J Sieben, Xiaolei Xu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Autophagy activators suppress cystogenesis in an autosomal dominant polycystic kidney disease model."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Mol Genet (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/hmg/ddw376"}], "href": "https://doi.org/10.1093/hmg/ddw376"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28007903"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28007903"}]}]}]}