{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T05:33:16Z","timestamp":1789450396720,"version":"build-2803163510"},"reference-count":67,"publisher":"American Society for Clinical Investigation","issue":"18","license":[{"start":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T00:00:00Z","timestamp":1789430400000},"content-version":"vor","delay-in-days":77,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,9,15]]},"abstract":"<jats:p>\n                    Autosomal dominant polycystic kidney disease (ADPKD), the leading genetic cause of kidney failure, results from loss-of-function mutations in\n                    <jats:italic>PKD1<\/jats:italic>\n                    , encoding polycystin-1 (PC1). PC1 localizes to the primary cilium. In the absence of PC1, adverse signaling from the primary cilium orchestrates cyst formation, but the biomechanical underpinnings of this cilia-dependent cyst activation (CDCA) remain unclear. Combining tubule-specific orthologous mouse models with a tubule-on-chip platform, we show that PC1 and cilia govern the composition, mechanical properties, and shape of the tubular basement membrane (TBM), the principal rigid determinant of tubule geometry. PC1 loss triggered TBM thinning, heparan sulfate enrichment, and deformation, leading to distension, preferentially of the distal nephron. These changes were driven by a cilia-dependent transcriptional program, with GLIS2 \u2014 a key CDCA effector \u2014 participating as a downstream mediator. Reduction of TBM stiffness amplified\n                    <jats:italic>Pkd1<\/jats:italic>\n                    <jats:sup>\u2013\/\u2013<\/jats:sup>\n                    tubule-on-chip dilation and increased cyst formation in vivo. Conversely, increasing luminal pressure through ureteral obstruction induced disproportionate distension of\n                    <jats:italic>Pkd1<\/jats:italic>\n                    -deficient tubules and triggered an irreversible cystogenic program. Together, these findings establish a TBM-centered biomechanical model of ADPKD in which tubule deformation is governed by both basolateral and luminal mechanical factors and identify the cilium\/TBM axis, operating in part through GLIS2, as a central driver of cystogenesis.\n                  <\/jats:p>","DOI":"10.1172\/jci196814","type":"journal-article","created":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T18:29:20Z","timestamp":1782844160000},"source":"Crossref","is-referenced-by-count":1,"title":["Cilia\u2013to\u2013basement membrane signaling is a biomechanical driver in models of autosomal dominant polycystic kidney disease"],"prefix":"10.1172","volume":"136","author":[{"given":"Manal","family":"Mazloum","sequence":"first","affiliation":[{"name":"Universit\u00e9 Paris Cit\u00e9, INSERM U1151, CNRS UMR 8235, Institut Necker Enfants Malades, D\u00e9partement Croissance et Signalisation, Paris, France."},{"name":"Assistance Publique-H\u00f4pitaux de Paris, H\u00f4pital 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