{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T05:05:15Z","timestamp":1780031115491,"version":"3.53.1"},"reference-count":71,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T00:00:00Z","timestamp":1780012800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Physiol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Transglutaminase 2 (TG2) plays a profibrotic role in chronic kidney disease (CKD), but its role in the exosomal proteome remains unexplored. Here, we aimed to evaluate biological processes specifically involved in CKD progression through exosomal proteomic profiling following TG2 inhibition.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and methods<\/jats:title>\n                    <jats:p>\n                      Human proximal tubular epithelial cells (hPTECs) were treated with recombinant transforming growth factor-\u03b2 (rTGF-\u03b2) to induce fibrosis and cysteamine to inhibit TG2. A unilateral ureteral obstruction (UUO) mouse model was used for\n                      <jats:italic>in vivo<\/jats:italic>\n                      validation. EVs were isolated and analyzed using LC-MS\/MS analysis. Bioinformatics tools, including enrichGO and STRING, were used to identify key biological pathways and protein interactions. Findings were validated in the UUO mouse model.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>TG2 inhibition attenuated the expression of fibrosis- and inflammation-associated proteins in hPTECs and fibroblasts. EV proteomic analysis revealed distinct protein expression patterns following rTGF-\u03b2 treatment and TG2 inhibition. Altered proteins were primarily extracellular matrix components such as connective tissue growth factor, IGF-binding protein, laminin, plasminogen activator inhibitor, periostin, and collagen.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>TG2 inhibition modulated EV-associated proteins involved in fibrosis and inflammation, highlighting its therapeutic potential in CKD. Identifying reversible fibrosis-related factors may provide new targets for CKD treatment.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fphys.2026.1786999","type":"journal-article","created":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T04:50:56Z","timestamp":1780030256000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["A comprehensive approach to elucidating the pathophysiology of kidney fibrosis based on extracellular vesicle proteomics"],"prefix":"10.3389","volume":"17","author":[{"given":"Yaerim","family":"Kim","sequence":"first","affiliation":[{"name":"Department of Internal Medicine, Keimyung University School of Medicine","place":["Daegu, Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyuhyeon","family":"Kim","sequence":"additional","affiliation":[{"name":"Biomedical Research Institute, Seoul National University","place":["Seoul, Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong-Beom","family":"Park","sequence":"additional","affiliation":[{"name":"Biomedical Research Institute, Seoul National University","place":["Seoul, Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sunwha","family":"Lee","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Internal Medicine, Kangwon National University Hospital","place":["Chuncheon, Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mi-yeon","family":"Yu","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Internal Medicine, Hanyang University Guri Hospital","place":["Guri, Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Young Joo","family":"Kim","sequence":"additional","affiliation":[{"name":"Biomedical Research Institute, Seoul National University","place":["Seoul, Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Soo Bin","family":"Choi","sequence":"additional","affiliation":[{"name":"Biomedical Research Institute, Seoul National University","place":["Seoul, Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Woo Yeong","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Keimyung University School of Medicine","place":["Daegu, Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyubok","family":"Jin","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Keimyung University School of Medicine","place":["Daegu, Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dong Ki","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Seoul National University College of Medicine","place":["Seoul, Republic of Korea"]},{"name":"Kidney Research Institute, Seoul National University College of Medicine","place":["Seoul, Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yon Su","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Seoul National University College of Medicine","place":["Seoul, Republic of Korea"]},{"name":"Kidney Research Institute, Seoul National University College of Medicine","place":["Seoul, Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dohyun","family":"Han","sequence":"additional","affiliation":[{"name":"Biomedical Research Institute, Seoul National University","place":["Seoul, Republic of Korea"]},{"name":"Proteomics Core Facility, Biomedical Research Institute, Seoul National University Hospital","place":["Seoul, Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seung Hee","family":"Yang","sequence":"additional","affiliation":[{"name":"Biomedical Research Institute, Seoul National University","place":["Seoul, Republic of Korea"]},{"name":"Kidney Research Institute, Seoul National University College of Medicine","place":["Seoul, Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,5,29]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"663","DOI":"10.1369\/0022155419852932","article-title":"Renal inflammation and fibrosis: a double-edged sword","volume":"67","author":"Black","year":"2019","journal-title":"J. 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