{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T07:14:58Z","timestamp":1781594098457,"version":"3.54.5"},"reference-count":73,"publisher":"American Society for Clinical Investigation","issue":"18","funder":[{"name":"European Foundation for the Study of Diabetes (EFSD)\/Novo Nordisk Programme 2017","award":["not applicable"],"award-info":[{"award-number":["not applicable"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2019,9,19]]},"abstract":"<jats:p>\n                    Thyroid hormone (TH) signaling is a universal regulator of metabolism, growth, and development. Here, we show that TH-TH receptor (TH-TR) axis alterations are critically involved in diabetic nephropathy\u2013associated (DN-associated) podocyte pathology, and we identify TR\u03b11 as a key regulator of the pathogenesis of DN. In ZSF1 diabetic rats, T\n                    <jats:sub>3<\/jats:sub>\n                    levels progressively decreased during DN, and this was inversely correlated with metabolic and renal disease worsening. These phenomena were associated with the reexpression of the fetal isoform TR\u03b11 in podocytes and parietal cells of both rats and patients with DN and with the increased glomerular expression of the TH-inactivating enzyme deiodinase 3 (DIO3). In diabetic rats, TR\u03b11-positive cells also reexpressed several fetal mesenchymal and damage-related podocyte markers, while glomerular and podocyte hypertrophy was evident. In vitro, exposing human podocytes to diabetes milieu typical components markedly increased TR\u03b11 and DIO3 expression and induced cytoskeleton rearrangements, adult podocyte marker downregulation and fetal kidney marker upregulation, the maladaptive cell cycle induction\/arrest, and TR\u03b11-ERK1\/2\u2013mediated hypertrophy. Strikingly, T\n                    <jats:sub>3<\/jats:sub>\n                    treatment reduced TR\u03b11 and DIO3 expression and completely reversed all these alterations. Our data show that diabetic stress induces the TH-TR\u03b11 axis to adopt a fetal ligand\/receptor relationship pattern that triggers the recapitulation of the fetal podocyte phenotype and subsequent pathological alterations.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.130249","type":"journal-article","created":{"date-parts":[[2019,9,18]],"date-time":"2019-09-18T11:00:55Z","timestamp":1568804455000},"source":"Crossref","is-referenced-by-count":35,"title":["Alteration of thyroid hormone signaling triggers the diabetes-induced pathological growth, remodeling, and dedifferentiation of podocytes"],"prefix":"10.1172","volume":"4","author":[{"given":"Valentina","family":"Benedetti","sequence":"first","affiliation":[{"name":"Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Centro Anna Maria Astori, Science and Technology Park Kilometro Rosso, Bergamo, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angelo Michele","family":"Lavecchia","sequence":"additional","affiliation":[{"name":"Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Centro Anna Maria Astori, Science and Technology Park Kilometro Rosso, Bergamo, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monica","family":"Locatelli","sequence":"additional","affiliation":[{"name":"Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Centro Anna Maria Astori, Science and Technology Park Kilometro Rosso, Bergamo, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valerio","family":"Brizi","sequence":"additional","affiliation":[{"name":"Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Centro Anna Maria Astori, Science and Technology Park Kilometro Rosso, Bergamo, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniela","family":"Corna","sequence":"additional","affiliation":[{"name":"Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Centro Anna Maria Astori, Science and Technology Park Kilometro Rosso, Bergamo, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta","family":"Todeschini","sequence":"additional","affiliation":[{"name":"Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Centro Anna Maria Astori, Science and Technology Park Kilometro Rosso, Bergamo, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rubina","family":"Novelli","sequence":"additional","affiliation":[{"name":"Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Centro Anna Maria Astori, Science and Technology Park Kilometro Rosso, Bergamo, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ariela","family":"Benigni","sequence":"additional","affiliation":[{"name":"Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Centro Anna Maria Astori, Science and Technology Park Kilometro Rosso, Bergamo, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlamaria","family":"Zoja","sequence":"additional","affiliation":[{"name":"Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Centro Anna Maria Astori, Science and Technology Park Kilometro Rosso, Bergamo, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppe","family":"Remuzzi","sequence":"additional","affiliation":[{"name":"Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Centro Anna Maria Astori, Science and Technology Park Kilometro Rosso, Bergamo, Italy."},{"name":"L. 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