{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T01:24:27Z","timestamp":1787016267931,"version":"build-2736575974"},"reference-count":49,"publisher":"Wiley","issue":"19","license":[{"start":{"date-parts":[[2024,8,15]],"date-time":"2024-08-15T00:00:00Z","timestamp":1723680000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2024,8,15]],"date-time":"2024-08-15T00:00:00Z","timestamp":1723680000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["physoc.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Physiology"],"published-print":{"date-parts":[[2024,10]]},"abstract":"<jats:sec>\n                    <jats:title>Abstract<\/jats:title>\n                    <jats:p>\n                      Ischaemia\u2010reperfusion (IR)\u2010associated acute kidney injury (AKI) is a severe clinical condition that lacks effective pharmacological treatments. Our recent research revealed that pretreatment with the angiotensin II type 2 receptor (AT2R) agonist C21 alleviates kidney damage during IR. Primary cilia are organelles crucial for regulation of epithelial cell homeostasis, which are significantly affected by IR injury. This study aimed to evaluate the impact of AT2R activation on cilia integrity during IR and to identify pathways involved in the nephroprotective effect of C21. Rats were subjected to 40\u00a0min of unilateral ischaemia followed by 24\u00a0h of reperfusion. Immunofluorescence analysis of the kidneys showed that the nephroprotective effect of C21 was associated with preservation of cilia integrity in tubular cells. AT2R agonists increased \u03b1\u2010tubulin acetylation in primary cilia in tubular cells\n                      <jats:italic>in vivo<\/jats:italic>\n                      and in a cell model. Analysis of ERK phosphorylation indicated that AT2R activation led to diminished activation of ERK1\/2 in tubular cells. Similar to AT2R agonists, inhibitors of \u03b1\u2010tubulin deacetylase HDAC6 or inhibitors of ERK activation ameliorated IR\u2010induced cell death and preserved cilia integrity. Immunofluorescence analysis of tubular cells revealed significant ERK localization at primary cilia and demonstrated that ERK inhibition increased cilia levels of acetylated \u03b1\u2010tubulin. Overall, our findings demonstrate that C21 elicits a preconditioning effect that enhances cilia stability in renal tubular cells, thereby preserving their integrity when exposed to IR injury. Furthermore, our results indicate that this effect might be mediated by AT2R\u2010induced inhibition of ERK activation. These findings offer potential insights for the development of pharmacological interventions to mitigate IR\u2010associated AKI.\n                      <jats:boxed-text content-type=\"graphic\" position=\"anchor\">\n                        <jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/tjp16247-gra-0001-m.png\">\n                          <jats:alt-text>image<\/jats:alt-text>\n                        <\/jats:graphic>\n                      <\/jats:boxed-text>\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Key points<\/jats:title>\n                    <jats:p>\n                      <jats:list list-type=\"bullet\">\n                        <jats:list-item>\n                          <jats:p>The AT2R agonist C21 prevents primary cilia shortening and tubular cell deciliation during renal ischaemia\u2010reperfusion.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>AT2R activation inhibits ERK1\/2 in renal tubular cells.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Both AT2R agonists and ERK1\/2 inhibitors increase alpha\u2010tubulin acetylation at the primary cilium in tubular cells.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>AT2R activation, ERK1\/2 inhibition or inhibition of alpha\u2010tubulin deacetylation elicit protective effects in tubular cells subjected to ischaemia\u2010reperfusion injury.<\/jats:p>\n                        <\/jats:list-item>\n                      <\/jats:list>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1113\/jp286514","type":"journal-article","created":{"date-parts":[[2024,8,15]],"date-time":"2024-08-15T14:28:51Z","timestamp":1723732131000},"page":"5083-5103","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Activation of angiotensin II type 2 receptor leads to preservation of primary cilia in tubular cells during renal ischaemia\u2010reperfusion injury"],"prefix":"10.1113","volume":"602","author":[{"given":"Tom\u00e1s Rivabella","family":"Maknis","sequence":"first","affiliation":[{"name":"Instituto de Fisiolog\u00eda Experimental, Consejo Nacional de Investigaciones Cient\u00edficas y T\u00e9cnicas (CONICET), Facultad de Ciencias Bioqu\u00edmicas y Farmac\u00e9uticas (FBIOyF) Universidad Nacional de Rosario (UNR)  Rosario Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-6007-5861","authenticated-orcid":false,"given":"M. Fernanda","family":"Fussi","sequence":"additional","affiliation":[{"name":"Instituto de Fisiolog\u00eda Experimental, Consejo Nacional de Investigaciones Cient\u00edficas y T\u00e9cnicas (CONICET), Facultad de Ciencias Bioqu\u00edmicas y Farmac\u00e9uticas (FBIOyF) Universidad Nacional de Rosario (UNR)  Rosario Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alejandro P.","family":"Pariani","sequence":"additional","affiliation":[{"name":"Instituto de Fisiolog\u00eda Experimental, Consejo Nacional de Investigaciones Cient\u00edficas y T\u00e9cnicas (CONICET), Facultad de Ciencias Bioqu\u00edmicas y Farmac\u00e9uticas (FBIOyF) Universidad Nacional de Rosario (UNR)  Rosario Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victoria","family":"Huhn","sequence":"additional","affiliation":[{"name":"Instituto de Fisiolog\u00eda Experimental, Consejo Nacional de Investigaciones Cient\u00edficas y T\u00e9cnicas (CONICET), Facultad de Ciencias Bioqu\u00edmicas y Farmac\u00e9uticas (FBIOyF) Universidad Nacional de Rosario (UNR)  Rosario Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rodrigo","family":"Vena","sequence":"additional","affiliation":[{"name":"Instituto de Biolog\u00eda Molecular y Celular de Rosario CONICET\u2010UNR  Rosario Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristi\u00e1n","family":"Favre","sequence":"additional","affiliation":[{"name":"Instituto de Fisiolog\u00eda Experimental, Consejo Nacional de Investigaciones Cient\u00edficas y T\u00e9cnicas (CONICET), Facultad de Ciencias Bioqu\u00edmicas y Farmac\u00e9uticas (FBIOyF) Universidad Nacional de Rosario (UNR)  Rosario Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara M.","family":"Molinas","sequence":"additional","affiliation":[{"name":"Instituto de Fisiolog\u00eda Experimental, Consejo Nacional de Investigaciones Cient\u00edficas y T\u00e9cnicas (CONICET), Facultad de Ciencias Bioqu\u00edmicas y Farmac\u00e9uticas (FBIOyF) Universidad Nacional de Rosario (UNR)  Rosario Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6967-5431","authenticated-orcid":false,"given":"M. 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