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A related secondary objective was to determine whether treatment of normal bladder epithelial cells with active synthetic asialo\u2010antiproliferative factor (\n                      <jats:italic>as<\/jats:italic>\n                      \u2010APF) induces similar changes in Akt signalling and specific downstream effector proteins\/mRNAs.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Patients and Methods<\/jats:title>\n                    <jats:p>Cell proteins were extracted into four subcellular fractions from primary bladder epithelial explants of six patients who fulfilled modified National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) criteria for IC\/BPS and six age\u2010 and gender\u2010matched controls. Total and\/or phosphorylated cellular Akt, glycogen synthase kinase 3\u03b2 (GSK3\u03b2), and \u03b2\u2010catenin; total cellular JunB; and secreted matrix metalloproteinase 2 (MMP2) and heparin\u2010binding epidermal growth factor\u2010like growth factor (HB\u2010EGF) levels were determined by Western blot. MMP2, JunB, p53, uroplakin 3 (UPK3), and \u03b2\u2010actin mRNAs were quantified by quantitative reverse transcriptase\u2010polymerase chain reaction. Akt activity was determined by nonradioactive assay.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      IC\/BPS cells had lower Akt activity, along with lower Akt ser473\u2010 and GSK3\u03b2 ser9\u2010phosphorylation and higher \u03b2\u2010catenin ser33,37\/thr41\u2010phosphorylation in specific fractions as compared with matched control cells. IC\/BPS explants also had evidence of additional downstream abnormalities compared with control cells, including lower nuclear JunB; lower secreted MMP2 and HB\u2010EGF; plus lower MMP2, JunB, and UPK3 mRNAs but higher p53 mRNA relative to \u03b2\u2010actin. Each of these IC\/BPS cell abnormalities was also induced in normal cells by\n                      <jats:italic>as<\/jats:italic>\n                      \u2010APF.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>These findings indicate that IC\/BPS cells have abnormal Akt activity with downstream protein expression abnormalities including decreased MMP2 and HB\u2010EGF secretion. They also support the hypothesis that APF plays a role in the pathogenesis of IC\/BPS via its effects on cell Akt signalling and HB\u2010EGF production.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/bju.13457","type":"journal-article","created":{"date-parts":[[2016,2,26]],"date-time":"2016-02-26T04:47:53Z","timestamp":1456462073000},"page":"161-172","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Abnormal Akt signalling in bladder epithelial cell explants from patients with interstitial cystitis\/bladder pain syndrome can be induced by antiproliferative factor treatment of normal bladder cells"],"prefix":"10.1111","volume":"118","author":[{"given":"Susan K.","family":"Keay","sequence":"first","affiliation":[{"name":"Department of Medicine Division of Infectious Diseases University of Maryland School of Medicine Baltimore MD USA"},{"name":"Department of Veterans Affairs Medical Center Medical Service 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