{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T03:16:58Z","timestamp":1773285418281,"version":"3.50.1"},"reference-count":44,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2019,12,23]],"date-time":"2019-12-23T00:00:00Z","timestamp":1577059200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000057","name":"National Institute of General Medical Sciences","doi-asserted-by":"publisher","award":["GM057242"],"award-info":[{"award-number":["GM057242"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["faseb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FASEB Journal"],"published-print":{"date-parts":[[2020,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>PPM1A and PTEN emerged as novel suppressors of chronic kidney disease (CKD). Since loss of PPM1A and PTEN in the tubulointerstitium promotes fibrogenesis, defining molecular events underlying PPM1A\/PTEN deregulation is necessary to develop expression rescue as novel therapeutic strategies. Here we identify TGF\u2010\u03b21 as a principle repressor of PPM1A, as conditional renal tubular\u2010specific induction of TGF\u2010\u03b21 in mice dramatically downregulates kidney PPM1A expression. TGF\u2010\u03b21 similarly attenuates PPM1A and PTEN expression in human renal epithelial cells and fibroblasts, via a protein degradation mechanism by promoting their ubiquitination. A proteasome inhibitor MG132 rescues PPM1A and PTEN expression, even in the presence of TGF\u2010\u03b21, along with decreased fibrogenesis. Restoration of PPM1A or PTEN similarly limits SMAD3 phosphorylation and the activation of TGF\u2010\u03b21\u2010induced fibrotic genes. Concurrent loss of PPM1A and PTEN levels in aristolochic acid nephropathy further suggests crosstalk between these repressors. PPM1A silencing in renal fibroblasts, moreover, results in PTEN loss, while PTEN stable depletion decreases PPM1A expression with acquisition of a fibroproliferative phenotype in each case. Transient PPM1A expression, conversely, elevates cellular PTEN levels while lentiviral PTEN introduction increases PPM1A expression. PPM1A and PTEN, therefore, co\u2010regulate each other's relative abundance, identifying a previously unknown pathological link between TGF\u2010\u03b21 repressors, contributing to CKD.<\/jats:p>","DOI":"10.1096\/fj.201902015rr","type":"journal-article","created":{"date-parts":[[2019,12,23]],"date-time":"2019-12-23T06:44:44Z","timestamp":1577083484000},"page":"2641-2656","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Protein phosphatase Mg\n                    <sup>2+<\/sup>\n                    \/Mn\n                    <sup>2+<\/sup>\n                    dependent\u20101A and PTEN deregulation in renal fibrosis: Novel mechanisms and co\u2010dependency of expression"],"prefix":"10.1096","volume":"34","author":[{"given":"Jiaqi","family":"Tang","sequence":"first","affiliation":[{"name":"Department of Regenerative and Cancer Cell Biology Albany Medical Center Albany NY USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Roel","family":"Goldschmeding","sequence":"additional","affiliation":[{"name":"Department of Pathology University Medical Center Utrecht Utrecht The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rohan","family":"Samarakoon","sequence":"additional","affiliation":[{"name":"Department of Regenerative and Cancer Cell Biology Albany Medical Center Albany NY USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paul J.","family":"Higgins","sequence":"additional","affiliation":[{"name":"Department of Regenerative and Cancer Cell Biology Albany Medical Center Albany NY USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2019,12,23]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1159\/000329385"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrneph.2010.120"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-pathol-020712-163930"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/path.4253"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.ackd.2005.07.011"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.3004700"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(13)60687-X"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1093\/ndt\/gfs284"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/ki.2011.368"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1093\/ndt\/gft267"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cellsig.2012.10.003"},{"issue":"4","key":"e_1_2_9_13_1","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1038\/kisup.2014.11","article-title":"Key fibrogenic mediators: old players. Renin\u2010angiotensin system","volume":"2011","author":"Macconi D","year":"2014","journal-title":"Kidney Int Suppl"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00441-011-1181-y"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrneph.2016.48"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cellsig.2013.07.007"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature02006"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cellsig.2014.02.017"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.14-262527"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.201700722R"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.201802489RR"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0400035101"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.ASN.0000099373.33259.B2"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.ki.5000261"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41580-018-0015-0"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers10060159"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncb1897"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI78945"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00660.2011"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1002\/path.4538"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2006.03.044"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.201500105R"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.2353\/ajpath.2010.091012"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1038\/ki.2008.129"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00675.2009"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-13486-x"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0042316"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajpath.2013.06.032"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1042\/CS20150427"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2014050463"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00081.2017"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbadis.2017.09.011"},{"key":"e_1_2_9_43_1","doi-asserted-by":"publisher","DOI":"10.1038\/jid.2011.156"},{"key":"e_1_2_9_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.matbio.2015.01.017"},{"key":"e_1_2_9_45_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.38121"}],"container-title":["The FASEB Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1096%2Ffj.201902015RR","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1096\/fj.201902015RR","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1096\/fj.201902015RR","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/faseb.onlinelibrary.wiley.com\/doi\/pdf\/10.1096\/fj.201902015RR","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,28]],"date-time":"2025-10-28T17:57:44Z","timestamp":1761674264000},"score":1,"resource":{"primary":{"URL":"https:\/\/faseb.onlinelibrary.wiley.com\/doi\/10.1096\/fj.201902015RR"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,12,23]]},"references-count":44,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2020,2]]}},"alternative-id":["10.1096\/fj.201902015RR"],"URL":"https:\/\/doi.org\/10.1096\/fj.201902015rr","archive":["Portico"],"relation":{},"ISSN":["0892-6638","1530-6860"],"issn-type":[{"value":"0892-6638","type":"print"},{"value":"1530-6860","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,12,23]]},"assertion":[{"value":"2019-08-07","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-12-05","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-12-23","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}