{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T19:45:32Z","timestamp":1768506332675,"version":"3.49.0"},"posted":{"date-parts":[[2023,5,3]]},"group-title":"Developmental Biology","reference-count":33,"publisher":"openRxiv","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2023,5,3]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Lymphangiogenesis is believed to be a protective response in the setting of multiple forms of kidney injury and mitigates the progression of interstitial fibrosis. To augment this protective response, promoting kidney lymphangiogenesis is being investigated as a potential treatment to slow the progression of kidney disease.<\/jats:p>\n                  <jats:p>As injury related lymphangiogenesis is driven by signaling from the receptor VEGFR-3 in response to the cognate growth factor VEGF-C released by tubular epithelial cells, this signaling pathway is a candidate for future kidney therapeutics. However, the consequences to kidney development and function to targeting this signaling pathway remains poorly defined.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>\n                    We generated a new mouse model expressing\n                    <jats:italic>Vegf-C<\/jats:italic>\n                    under regulation of the nephron progenitor Six2Cre driver strain (\n                    <jats:italic>Six2Vegf-C<\/jats:italic>\n                    ). Mice underwent a detailed phenotypic evaluation. Whole kidneys were processed for histology and micro computed tomography 3-dimensional imaging.\n                  <\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>\n                    <jats:italic>Six2Vegf-C<\/jats:italic>\n                    mice had reduced body weight and kidney function compared to littermate controls.\n                    <jats:italic>Six2Vegf-C<\/jats:italic>\n                    kidneys demonstrated large peripelvic fluid filled lesions with distortion of the pelvicalcyceal system which progressed in severity with age. 3D imaging showed a 3-fold increase in total cortical vascular density. Histology confirmed a substantial increase in LYVE1+\/PDPN+\/VEGFR3+ lymphatic capillaries extending alongside EMCN+ peritubular capillaries. There was no change in EMCN+ peritubular capillary density.\n                  <\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>\n                    Kidney lymphangiogenesis was robustly induced in the\n                    <jats:italic>Six2Vegf-C<\/jats:italic>\n                    mice. There were no changes in peritubular blood capillary density despite these endothelial cells also expressing VEGFR-3. The model resulted in a severe cystic kidney phenotype that resembled a human condition termed renal lymphangiectasia. This study defines the vascular consequences of augmenting VEGF-C signaling during kidney development and provides new insight into a mimicker of human cystic kidney disease.\n                  <\/jats:p>\n                <\/jats:sec>","DOI":"10.1101\/2023.05.03.538868","type":"posted-content","created":{"date-parts":[[2023,5,3]],"date-time":"2023-05-03T22:20:20Z","timestamp":1683152420000},"source":"Crossref","is-referenced-by-count":3,"title":["VEGF-C overexpression in kidney progenitor cells is a model of renal lymphangiectasia"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9470-648X","authenticated-orcid":false,"given":"Michael D.","family":"Donnan","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6720-8517","authenticated-orcid":false,"given":"Dilip K.","family":"Deb","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Valentin","family":"David","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3706-5727","authenticated-orcid":false,"given":"Susan E.","family":"Quaggin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"54368","reference":[{"key":"2023050513200439000_2023.05.03.538868v1.1","doi-asserted-by":"publisher","DOI":"10.1038\/s41581-018-0098-z"},{"key":"2023050513200439000_2023.05.03.538868v1.2","doi-asserted-by":"publisher","DOI":"10.1038\/ki.2008.661"},{"key":"2023050513200439000_2023.05.03.538868v1.3","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-019-1436-1"},{"key":"2023050513200439000_2023.05.03.538868v1.4","doi-asserted-by":"publisher","DOI":"10.1038\/labinvest.2017.77"},{"key":"2023050513200439000_2023.05.03.538868v1.5","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2014090856"},{"key":"2023050513200439000_2023.05.03.538868v1.6","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-6143.2006.01638.x"},{"key":"2023050513200439000_2023.05.03.538868v1.7","doi-asserted-by":"publisher","DOI":"10.1038\/s41581-021-00438-y"},{"key":"2023050513200439000_2023.05.03.538868v1.8","doi-asserted-by":"publisher","DOI":"10.14814\/phy2.15094"},{"key":"2023050513200439000_2023.05.03.538868v1.9","doi-asserted-by":"publisher","DOI":"10.1097\/MNH.0000000000000717"},{"key":"2023050513200439000_2023.05.03.538868v1.10","doi-asserted-by":"publisher","DOI":"10.1038\/75997"},{"key":"2023050513200439000_2023.05.03.538868v1.11","doi-asserted-by":"publisher","DOI":"10.1038\/ni1013"},{"key":"2023050513200439000_2023.05.03.538868v1.12","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.92.8.3566"},{"key":"2023050513200439000_2023.05.03.538868v1.13","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.02214-07"},{"key":"2023050513200439000_2023.05.03.538868v1.14","doi-asserted-by":"publisher","DOI":"10.1242\/dev.122.12.3829"},{"key":"2023050513200439000_2023.05.03.538868v1.15","doi-asserted-by":"publisher","DOI":"10.1038\/ki.2012.312"},{"key":"2023050513200439000_2023.05.03.538868v1.16","doi-asserted-by":"publisher","DOI":"10.1038\/s41374-019-0259-0"},{"key":"2023050513200439000_2023.05.03.538868v1.17","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajpath.2017.04.007"},{"key":"2023050513200439000_2023.05.03.538868v1.18","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-020-03385-x"},{"key":"2023050513200439000_2023.05.03.538868v1.19","doi-asserted-by":"publisher","DOI":"10.1016\/j.kint.2019.07.027"},{"key":"2023050513200439000_2023.05.03.538868v1.20","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00066.2022"},{"key":"2023050513200439000_2023.05.03.538868v1.21","doi-asserted-by":"publisher","DOI":"10.7759\/cureus.10849"},{"key":"2023050513200439000_2023.05.03.538868v1.22","doi-asserted-by":"publisher","DOI":"10.1093\/ndt\/12.8.1701"},{"key":"2023050513200439000_2023.05.03.538868v1.23","doi-asserted-by":"publisher","DOI":"10.1016\/j.ekir.2021.03.005"},{"key":"2023050513200439000_2023.05.03.538868v1.24","doi-asserted-by":"publisher","DOI":"10.1016\/j.kint.2022.04.005"},{"key":"2023050513200439000_2023.05.03.538868v1.25","doi-asserted-by":"publisher","DOI":"10.1007\/s00441-010-1098-x"},{"key":"2023050513200439000_2023.05.03.538868v1.26","doi-asserted-by":"publisher","DOI":"10.1007\/s10157-012-0637-z"},{"key":"2023050513200439000_2023.05.03.538868v1.27","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.48183"},{"key":"2023050513200439000_2023.05.03.538868v1.28","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V96.12.3793"},{"key":"2023050513200439000_2023.05.03.538868v1.29","doi-asserted-by":"publisher","DOI":"10.1242\/dev.160184"},{"key":"2023050513200439000_2023.05.03.538868v1.30","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2008.05.020"},{"key":"2023050513200439000_2023.05.03.538868v1.31","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M109.050906"},{"key":"2023050513200439000_2023.05.03.538868v1.32","doi-asserted-by":"publisher","DOI":"10.1002\/jbmr.4540"},{"key":"2023050513200439000_2023.05.03.538868v1.33","doi-asserted-by":"publisher","DOI":"10.1016\/j.bone.2011.09.051"}],"container-title":[],"original-title":[],"link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1101\/2023.05.03.538868","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T04:37:03Z","timestamp":1768451823000},"score":1,"resource":{"primary":{"URL":"http:\/\/biorxiv.org\/lookup\/doi\/10.1101\/2023.05.03.538868"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,5,3]]},"references-count":33,"URL":"https:\/\/doi.org\/10.1101\/2023.05.03.538868","relation":{},"subject":[],"published":{"date-parts":[[2023,5,3]]},"subtype":"preprint"}}