{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T13:07:00Z","timestamp":1779196020391,"version":"3.51.4"},"reference-count":61,"publisher":"American Society for Clinical Investigation","issue":"13","funder":[{"DOI":"10.13039\/501100003977","name":"Israel Science Foundation","doi-asserted-by":"crossref","award":["2358\/18"],"award-info":[{"award-number":["2358\/18"]}],"id":[{"id":"10.13039\/501100003977","id-type":"DOI","asserted-by":"crossref"}]},{"name":"institutional grants from the Hadassah-Hebrew University Medical Center","award":["Startup"],"award-info":[{"award-number":["Startup"]}]},{"name":"institutional grants from the Hadassah-Hebrew University Medical Center","award":["bridging grants"],"award-info":[{"award-number":["bridging grants"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,7,9]]},"abstract":"<jats:p>\n                    Chronic kidney disease is the main cause of mortality in patients with tuberous sclerosis complex (TSC) disease. The mechanisms underlying TSC cystic kidney disease remain unclear, with no available interventions to prevent cyst formation. Using targeted deletion of\n                    <jats:italic>TSC1<\/jats:italic>\n                    in nephron progenitor cells, we showed that cysts in\n                    <jats:italic>TSC1-<\/jats:italic>\n                    null embryonic kidneys originate from injured proximal tubular cells with high mTOR complex 1 activity. Injection of rapamycin to pregnant mice inhibited the mTOR pathway and tubular cell proliferation in kidneys of\n                    <jats:italic>TSC1<\/jats:italic>\n                    -null offspring. Rapamycin also prevented renal cystogenesis and prolonged the life span of TSC newborns. Gene expression analysis of proximal tubule cells identified sets of genes and pathways that were modified secondary to\n                    <jats:italic>TSC1<\/jats:italic>\n                    deletion and rescued by rapamycin administration during nephrogenesis. Inflammation with mononuclear infiltration was observed in the cystic areas of\n                    <jats:italic>TSC1-<\/jats:italic>\n                    null kidneys. Dexamethasone administration during pregnancy decreased cyst formation by not only inhibiting the inflammatory response, but also interfering with the mTORC1 pathway. These results reveal mechanisms of cystogenesis in TSC disease and suggest interventions before birth to ameliorate cystic disease in offspring.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.136857","type":"journal-article","created":{"date-parts":[[2020,6,2]],"date-time":"2020-06-02T12:04:48Z","timestamp":1591099488000},"source":"Crossref","is-referenced-by-count":6,"title":["Rapamycin and dexamethasone during pregnancy prevent tuberous sclerosis complex\u2013associated cystic kidney disease"],"prefix":"10.1172","volume":"5","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7683-4448","authenticated-orcid":true,"given":"Morris","family":"Nechama","sequence":"first","affiliation":[{"name":"Pediatric Nephrology Unit and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yaniv","family":"Makayes","sequence":"additional","affiliation":[{"name":"Pediatric Nephrology Unit 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