{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T03:31:19Z","timestamp":1793331079789,"version":"4.5.0"},"reference-count":68,"publisher":"American Society for Clinical Investigation","issue":"19","license":[{"start":{"date-parts":[[2021,10,8]],"date-time":"2021-10-08T00:00:00Z","timestamp":1633651200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000968","name":"American Heart Association","doi-asserted-by":"crossref","award":["AHASDG25870018"],"award-info":[{"award-number":["AHASDG25870018"]}],"id":[{"id":"10.13039\/100000968","id-type":"DOI","asserted-by":"crossref"}]},{"name":"NIH","award":["RO1-DK122164"],"award-info":[{"award-number":["RO1-DK122164"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,10,8]]},"abstract":"<jats:p>Herein, we report that Shroom3 knockdown, via Fyn inhibition, induced albuminuria with foot process effacement (FPE) without focal segmental glomerulosclerosis (FSGS) or podocytopenia. Interestingly, knockdown mice had reduced podocyte volumes. Human minimal change disease (MCD), where podocyte Fyn inactivation was reported, also showed lower glomerular volumes than FSGS. We hypothesized that lower glomerular volume prevented the progression to podocytopenia. To test this hypothesis, we utilized unilateral and 5\/6th nephrectomy models in Shroom3-KD mice. Knockdown mice exhibited less glomerular and podocyte hypertrophy after nephrectomy. FYN-knockdown podocytes had similar reductions in podocyte volume, implying that Fyn was downstream of Shroom3. Using SHROOM3 or FYN knockdown, we confirmed reduced podocyte protein content, along with significantly increased phosphorylated AMPK, a negative regulator of anabolism. AMPK activation resulted from increased cytoplasmic redistribution of LKB1 in podocytes. Inhibition of AMPK abolished the reduction in glomerular volume and induced podocytopenia in mice with FPE, suggesting a protective role for AMPK activation. In agreement with this, treatment of glomerular injury models with AMPK activators restricted glomerular volume, podocytopenia, and progression to FSGS. Glomerular transcriptomes from MCD biopsies also showed significant enrichment of Fyn inactivation and Ampk activation versus FSGS glomeruli. In summary, we demonstrated the important role of AMPK in glomerular volume regulation and podocyte survival. Our data suggest that AMPK activation adaptively regulates glomerular volume to prevent podocytopenia in the context of podocyte injury.<\/jats:p>","DOI":"10.1172\/jci.insight.150004","type":"journal-article","created":{"date-parts":[[2021,9,2]],"date-time":"2021-09-02T12:01:57Z","timestamp":1630584117000},"source":"Crossref","is-referenced-by-count":26,"title":["AMPK mediates regulation of glomerular volume and podocyte survival"],"prefix":"10.1172","volume":"6","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6680-2688","authenticated-orcid":true,"given":"Khadija","family":"Banu","sequence":"first","affiliation":[{"name":"Division of Nephrology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York, USA."},{"name":"Division of Nephrology, Department of Medicine, Yale University School of Medicine, New Haven, Connecticut, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5149-2717","authenticated-orcid":true,"given":"Qisheng","family":"Lin","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York, USA."},{"name":"Department of Nephrology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7447-2129","authenticated-orcid":true,"given":"John M.","family":"Basgen","sequence":"additional","affiliation":[{"name":"Morphometry and Stereology Laboratory, Charles R. Drew University of Medicine and Science, Los Angeles, California, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marina","family":"Planoutene","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chengguo","family":"Wei","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5656-0205","authenticated-orcid":true,"given":"Anand C.","family":"Reghuvaran","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Medicine, Yale University School of Medicine, New Haven, Connecticut, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuefei","family":"Tian","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Medicine, Yale University School of Medicine, New Haven, Connecticut, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongmei","family":"Shi","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Medicine, Yale University School of Medicine, New Haven, Connecticut, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Felipe","family":"Garzon","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6270-1369","authenticated-orcid":true,"given":"Aitor","family":"Garzia","sequence":"additional","affiliation":[{"name":"Laboratory of RNA Molecular Biology, The Rockefeller University, New York, New York, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6884-3686","authenticated-orcid":true,"given":"Nicholas","family":"Chun","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arun","family":"Cumpelik","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4575-5330","authenticated-orcid":true,"given":"Andrew D.","family":"Santeusanio","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Medicine, Yale University School of Medicine, New Haven, Connecticut, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weijia","family":"Zhang","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bhaskar","family":"Das","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2603-2778","authenticated-orcid":true,"given":"Fadi","family":"Salem","sequence":"additional","affiliation":[{"name":"Department of Pathology, Icahn School of Medicine at Mount Sinai, New York, New York, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3833-2583","authenticated-orcid":true,"given":"Li","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Pathology, Icahn School of Medicine at Mount Sinai, New York, New York, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3212-641X","authenticated-orcid":true,"given":"Shuta","family":"Ishibe","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Medicine, Yale University School of Medicine, New Haven, Connecticut, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lloyd G.","family":"Cantley","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Medicine, Yale University School of Medicine, New Haven, Connecticut, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lewis","family":"Kaufman","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8342-5458","authenticated-orcid":true,"given":"Kevin V.","family":"Lemley","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Children\u2019s Hospital Los Angeles, University of Southern California, Los Angeles, California, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhaohui","family":"Ni","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John Cijiang","family":"He","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3608-5638","authenticated-orcid":true,"given":"Barbara","family":"Murphy","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9567-4299","authenticated-orcid":true,"given":"Madhav C.","family":"Menon","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York, USA."},{"name":"Division of Nephrology, Department of Medicine, Yale University School of Medicine, New Haven, Connecticut, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"232","published-online":{"date-parts":[[2021,10,8]]},"reference":[{"key":"B1","doi-asserted-by":"crossref","DOI":"10.1155\/2012\/749010","article-title":"The glomerular filtration barrier: components and crosstalk","volume":"2012","author":"Menon","year":"2012","journal-title":"Int J Nephrol"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1038\/nrneph.2016.147"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.2215\/CJN.05760515"},{"issue":"18","key":"B4","doi-asserted-by":"crossref","DOI":"10.1172\/jci.insight.99271","article-title":"mTOR-mediated podocyte hypertrophy regulates glomerular integrity in mice and humans","volume":"4","author":"Puelles","year":"2019","journal-title":"JCI Insight"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0157148"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1016\/j.kint.2018.08.013"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2016111166"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2017020174"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1172\/JCI76902"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2018060573"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2017080856"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1101\/gr.182881.114"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M301689200"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2009-11-251132"},{"issue":"122","key":"B15","doi-asserted-by":"crossref","DOI":"10.1126\/scisignal.2000678","article-title":"c-mip impairs podocyte proximal signaling and induces heavy proteinuria","volume":"3","author":"Zhang","year":"2010","journal-title":"Sci Signal"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1038\/ki.2012.428"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2011.03.012"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1016\/j.toxlet.2013.11.031"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2013070798"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1046\/j.1523-1755.1999.00407.x"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2009.12.010"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1016\/j.cellsig.2017.05.010"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.117.311159"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2011020200"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1038\/nature07536"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00011.2008"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1111\/acel.12338"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1011498108"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1089\/thy.2013.0041"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1172\/JCI13505"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M409985200"},{"issue":"6","key":"B32","doi-asserted-by":"crossref","DOI":"10.1111\/eci.13247","article-title":"The AMP-activated protein kinase modulates hypothermia-induced J wave","volume":"50","author":"Wu","year":"2020","journal-title":"Eur J Clin Invest"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2014111131"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkw377"},{"key":"B35","doi-asserted-by":"crossref","DOI":"10.1038\/emm.2013.65","article-title":"AMP-activated protein kinase as a key molecular link between metabolism and clockwork","volume":"45","author":"Lee","year":"2013","journal-title":"Exp Mol Med"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.C700070200"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1038\/sj.emboj.7600110"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1126\/science.1075762"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M710372200"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1126\/science.aar2131"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1038\/nrm.2017.95"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2005010055"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2014030287"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1016\/j.semnephrol.2015.04.004"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1016\/j.ceb.2017.01.005"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1080\/15548627.2019.1705007"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1126\/science.1196371"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00114.2017"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2011010026"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.1172\/JCI66218"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00293.2013"},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00539.2019"},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00278.2006"},{"key":"B54","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.25598"},{"key":"B55","doi-asserted-by":"publisher","DOI":"10.1038\/kisup.2014.21"},{"key":"B56","doi-asserted-by":"publisher","DOI":"10.2337\/dc19-0936"},{"key":"B57","doi-asserted-by":"publisher","DOI":"10.1038\/nm.4242"},{"key":"B58","doi-asserted-by":"publisher","DOI":"10.1038\/nm.2411"},{"key":"B59","doi-asserted-by":"publisher","DOI":"10.1172\/JCI71195"},{"key":"B60","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2019020111"},{"key":"B61","doi-asserted-by":"publisher","DOI":"10.1172\/JCI23348"},{"key":"B62","doi-asserted-by":"publisher","DOI":"10.1038\/s41573-019-0019-2"},{"key":"B63","unstructured":"Wallace PD, Das Bhaskar C. LkB1-ampk activators for therapeutic use in polycystic kidney disease. https:\/\/pubchem.ncbi.nlm.nih.gov\/patent\/US2017334892#section=Patent-Submission-Date Accessed September 9, 2021"},{"key":"B64","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.11916"},{"key":"B65","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2015.11.003"},{"key":"B66","doi-asserted-by":"publisher","DOI":"10.1023\/A:1020884312053"},{"key":"B67"},{"key":"B68","doi-asserted-by":"publisher","DOI":"10.1159\/000322701"}],"container-title":["JCI Insight"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/insight.jci.org\/articles\/view\/150004\/files\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,18]],"date-time":"2026-05-18T23:44:26Z","timestamp":1779147866000},"score":1,"resource":{"primary":{"URL":"https:\/\/insight.jci.org\/articles\/view\/150004"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,10,8]]},"references-count":68,"journal-issue":{"issue":"19","published-online":{"date-parts":[[2021,10,8]]},"published-print":{"date-parts":[[2021,10,8]]}},"alternative-id":["10.1172\/jci.insight.150004"],"URL":"https:\/\/doi.org\/10.1172\/jci.insight.150004","relation":{},"ISSN":["2379-3708"],"issn-type":[{"value":"2379-3708","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,10,8]]},"article-number":"e150004"}}