{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T01:14:57Z","timestamp":1787015697239,"version":"build-2736575974"},"reference-count":30,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2020,7,17]],"date-time":"2020-07-17T00:00:00Z","timestamp":1594944000000},"content-version":"am","delay-in-days":352,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#am"},{"start":{"date-parts":[[2019,7,31]],"date-time":"2019-07-31T00:00:00Z","timestamp":1564531200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["1083131"],"award-info":[{"award-number":["1083131"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["1117017"],"award-info":[{"award-number":["1117017"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000923","name":"Australian Research Council","doi-asserted-by":"publisher","award":["CE140100011"],"award-info":[{"award-number":["CE140100011"]}],"id":[{"id":"10.13039\/501100000923","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Nephrology"],"published-print":{"date-parts":[[2019,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aim<\/jats:title>\n                    <jats:p>Protease\u2010activated receptor 2 (PAR2) has been implicated in the development of renal inflammation and fibrosis. In particular, activation of PAR2 in cultured tubular epithelial cells induces extracellular signal\u2010regulated kinase signalling and secretion of fibronectin, C\u2013C Motif Chemokine Ligand 2 (CCL2) and transforming growth factor\u2010\u03b21 (TGF\u2010\u03b21), suggesting a role in tubulointerstitial inflammation and fibrosis. We tested this hypothesis in unilateral ureteric obstruction (UUO) in which ongoing tubular epithelial cell damage drives tubulointerstitial inflammation and fibrosis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Unilateral ureteric obstruction surgery was performed in groups (\n                      <jats:italic>n<\/jats:italic>\n                      = 9\/10) of\n                      <jats:italic>Par2\u2212\/\u2212<\/jats:italic>\n                      and wild type (WT) littermate mice which were killed 7\u2009days later. Non\u2010experimental mice were controls.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Wild type mice exhibited a 5\u2010fold increase in\n                      <jats:italic>Par2<\/jats:italic>\n                      messenger RNA (mRNA) levels in the UUO kidney.\n                      <jats:italic>In situ<\/jats:italic>\n                      hybridization localized\n                      <jats:italic>Par2<\/jats:italic>\n                      mRNA expression to tubular epithelial cells in normal kidney, with a marked increase in\n                      <jats:italic>Par2<\/jats:italic>\n                      mRNA expression by tubular cells, including damaged tubular cells, in WT UUO kidney. Tubular damage (tubular dilation, increased KIM\u20101 and decreased \u03b1\u2010Klotho expression) and tubular signalling (extracellular signal\u2010regulated kinase phosphorylation) seen in WT UUO were not altered in\n                      <jats:italic>Par2\u2212\/\u2212<\/jats:italic>\n                      UUO. In addition, macrophage infiltration, up\u2010regulation of M1 (NOS2) and M2 (CD206) macrophage markers, and up\u2010regulation of pro\u2010inflammatory molecules (tumour necrosis factor, CCL2, interleukin\u201036\u03b1) in WT UUO kidney were unchanged in\n                      <jats:italic>Par2\u2212\/\u2212<\/jats:italic>\n                      UUO. Finally, the accumulation of \u03b1\u2010SMA+ myofibroblasts, deposition of collagen IV and expression of pro\u2010fibrotic factors (CTGF, TGF\u2010\u03b21) were not different between WT and\n                      <jats:italic>Par2\u2212\/\u2212<\/jats:italic>\n                      UUO mice.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Protease\u2010activated receptor 2 expression is substantially up\u2010regulated in tubular epithelial cells in the obstructed kidney, but this does not contribute to the development of tubular damage, renal inflammation or fibrosis.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/nep.13635","type":"journal-article","created":{"date-parts":[[2019,7,17]],"date-time":"2019-07-17T11:38:57Z","timestamp":1563363537000},"page":"983-991","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Protease\u2010activated receptor 2 does not contribute to renal inflammation or fibrosis in the obstructed kidney"],"prefix":"10.1111","volume":"24","author":[{"given":"Frank Y","family":"Ma","sequence":"first","affiliation":[{"name":"Department of Nephrology, Monash Medical Centre Monash University  Melbourne Victoria Australia"},{"name":"Centre for Inflammatory Diseases Monash University  Melbourne Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingjie","family":"Han","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Monash Medical Centre Monash University  Melbourne Victoria Australia"},{"name":"Centre for Inflammatory 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