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However, little is known about how these mutations alter podocyte biology although a role in podocyte differentiation has been proposed (Yu S, et al. Exp Mol Med. 52(4):594\u2013603,2020).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      To explore the role of PLC\u03b5 in podocytes, A conditionally immortalised human podocyte cell line was generated from a patient with early onset NS, due to a nonsense\n                      <jats:italic>PLC\u03951<\/jats:italic>\n                      mutation, resulting histologically in diffuse mesangial sclerosis (DMS).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      In comparison to wild type podocytes, the\n                      <jats:italic>PLC\u03951<\/jats:italic>\n                      mutant podocyte cell has reduced epithelial features, altered actin cytoskeleton and significantly lower levels of the epithelial marker ZO-1.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      We demonstrate that PLC\u03b5 deficiency is associated with functionally impaired TGF-\u03b21 responses with an altered SMAD2\/SMAD3 ratio and absent SMAD2 phosphorylation, resulting in loss of the motility response to TGF-\u03b21. We further show that\n                      <jats:italic>PLCE1<\/jats:italic>\n                      knockdown in wild-type podocytes recapitulates this phenotype by knock-down of\n                      <jats:italic>PLC\u03951<\/jats:italic>\n                      in wild-type podocytes.\n                    <\/jats:p>\n                    <jats:p>\n                      This work reveals that disease-causing mutations in\n                      <jats:italic>PLC\u03951<\/jats:italic>\n                      result in podocyte dedifferentiation and uncovers a novel association between\n                      <jats:italic>PLC\u03951<\/jats:italic>\n                      deficiency and SMAD2\/3 signalling signalling in maintaining podocyte differentiation.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s12964-026-02867-3","type":"journal-article","created":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T23:13:51Z","timestamp":1778714031000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["PLC\u03b5 regulates podocyte differentiation and TGF-\u03b21 responses via alteration of SMAD2\/SMAD3 ratio"],"prefix":"10.1186","volume":"24","author":[{"given":"Carl J","family":"May","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah E","family":"Hunter","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Agnieszka","family":"Bierzynska","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lan","family":"Ni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katherine R","family":"Bull","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aneesha","family":"Bhandari","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gavin I","family":"Welsh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Moin A","family":"Saleem","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,5,14]]},"reference":[{"key":"2867_CR1","first-page":"226","volume":"5","author":"A Bierzynska","year":"2014","unstructured":"Bierzynska A, Soderquest K, Koziell A. 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