{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T20:30:39Z","timestamp":1768509039842,"version":"3.49.0"},"posted":{"date-parts":[[2024,3,3]]},"group-title":"Genetics","reference-count":45,"publisher":"openRxiv","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2024,3,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                <jats:p>\n                  Nephronophthisis (NPHP) and autosomal dominant Polycystic Kidney Disease (ADPKD) are two genetically distinct forms of Polycystic Kidney Disease (PKD), yet both diseases present with kidney cysts and a gradual decline in renal function. Prevailing dogma in PKD is that changes in kidney architecture account for the decline in kidney function, but the molecular\/cellular basis of such coupling is unknown. To address this question, we induced a form of proteome reprogramming by deleting\n                  <jats:italic>Fbxw7<\/jats:italic>\n                  encoding FBW7, the recognition receptor of the SCF\n                  <jats:sup>FBW7<\/jats:sup>\n                  E3 ubiquitin ligase in different segments of the kidney tubular system. Deletion of\n                  <jats:italic>Fbxw7<\/jats:italic>\n                  in the medulla led to a juvenile-adult NPHP-like phenotype, where the decline in renal function was due to SOX9-mediated interstitial fibrosis rather than cystogenesis. In contrast, the decline of renal function in ADPKD is coupled to cystic expansion via the abnormal accumulation of FBW7 in the proximal tubules and other cell types in the renal cortex. We propose that FBW7 functions at the apex of a protein network that determines renal function in ADPKD by sensing architectural changes induced by cystic expansion.\n                <\/jats:p>","DOI":"10.1101\/2024.02.29.582788","type":"posted-content","created":{"date-parts":[[2024,3,3]],"date-time":"2024-03-03T04:30:10Z","timestamp":1709440210000},"source":"Crossref","is-referenced-by-count":0,"title":["Nephronophthisis-associated FBW7 mediates cyst-dependent decline of renal function in ADPKD"],"prefix":"10.64898","author":[{"given":"Maulin Mukeshchandra","family":"Patel","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vasileios","family":"Gerakopoulos","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eleni","family":"Petsouki","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kurt A.","family":"Zimmerman","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Leonidas","family":"Tsiokas","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"54368","reference":[{"key":"2024030603000883000_2024.02.29.582788v1.1","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1038\/s41572-018-0047-y","article-title":"Polycystic kidney disease","volume":"4","year":"2018","journal-title":"Nat Rev Dis Primers"},{"key":"2024030603000883000_2024.02.29.582788v1.2","unstructured":"Harris, P.C. & Torres, V.E. Polycystic Kidney Disease, Autosomal Dominant. in GeneReviews((R)) (eds. Adam, M.P. et al.) (Seattle (WA), 1993)."},{"key":"2024030603000883000_2024.02.29.582788v1.3","unstructured":"Sweeney, W.E. & Avner, E.D. Polycystic Kidney Disease, Autosomal Recessive. in GeneReviews((R)) (eds. Adam, M.P. et al.) (Seattle (WA), 1993)."},{"key":"2024030603000883000_2024.02.29.582788v1.4","doi-asserted-by":"crossref","first-page":"166348","DOI":"10.1016\/j.bbadis.2022.166348","article-title":"The genetics of Autosomal Recessive Polycystic Kidney Disease (ARPKD)","volume":"1868","year":"2022","journal-title":"Biochim Biophys Acta Mol Basis Dis"},{"key":"2024030603000883000_2024.02.29.582788v1.5","unstructured":"Goksu, S.Y. , Leslie, S.W. & Khattar, D. Renal Cystic Disease. in StatPearls (Treasure Island (FL), 2024)."},{"key":"2024030603000883000_2024.02.29.582788v1.6","unstructured":"Stokman, M. , Lilien, M. & Knoers, N. Nephronophthisis-Related Ciliopathies. in GeneReviews((R)) (eds. 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