{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T22:05:30Z","timestamp":1790805930182,"version":"4.1.0"},"reference-count":55,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,4,26]],"date-time":"2026-04-26T00:00:00Z","timestamp":1777161600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100001296","name":"The PKD Foundation","doi-asserted-by":"crossref","award":["1021264"],"award-info":[{"award-number":["1021264"]}],"id":[{"id":"10.13039\/100001296","id-type":"DOI","asserted-by":"crossref"}]},{"award":["1021264"],"award-info":[{"award-number":["1021264"]}],"id":[{"id":"https:\/\/ror.org\/05g0xkn45","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","award":["R15DK137195"],"award-info":[{"award-number":["R15DK137195"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]},{"award":["R15DK137195"],"award-info":[{"award-number":["R15DK137195"]}],"id":[{"id":"https:\/\/ror.org\/00adh9b73","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Polycystic kidney disease (PKD), the most common inherited kidney disorder, is characterized by progressive cyst growth and eventual organ failure. Although aberrant innate immune activation is a recognized contributor to PKD progression, the underlying molecular mechanisms remain incompletely defined. Here, we showed that Pkd1 deletion increased TLR2 and MyD88 mRNA expression in renal epithelial cells, indicating enhanced innate immune priming. In vivo, administration of Pam3CSK4 (PAM), a synthetic TLR2 agonist, preferentially amplified pro-inflammatory and pro-fibrotic responses in Pkd1RC\/RC mice compared with wild-type controls, despite inducing similar signaling responses in vitro. Acute PAM treatment for one week rapidly enhanced NF-\u03baB activation in cyst-lining epithelial cells, increased renal inflammation and cell proliferation, and was associated with activation of mTOR signaling and upregulation of c-Myc and Wnt proteins. Sustained PAM treatment further accelerated cyst expansion and renal fibrosis in PKD mice. Importantly, the endogenous TLR2 ligands decorin and biglycan were markedly elevated in human PKD kidneys, supporting the translational relevance of enhanced TLR2 signaling in disease progression. Together, these findings suggest that TLR2 signaling is an important contributor to PKD progression and a potential therapeutic target.<\/jats:p>","DOI":"10.3390\/ijms27093853","type":"journal-article","created":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T11:33:37Z","timestamp":1777376017000},"page":"3853","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["TLR2 Activation Enhances Inflammatory Signaling and Accelerates Cyst Growth and Renal Fibrosis in Polycystic Kidney Disease Mice"],"prefix":"10.3390","volume":"27","author":[{"given":"Aiping","family":"Wei","sequence":"first","affiliation":[{"name":"Department of Anesthesiology, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang 330006, China"},{"name":"Department of Biological Science, College of Sciences and Arts, Michigan Technological University, Houghton, MI 49931, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang 330006, China"},{"name":"Department of Biological Science, College of Sciences and Arts, Michigan Technological University, Houghton, MI 49931, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang 330006, China"},{"name":"Department of Biological Science, College of Sciences and Arts, Michigan Technological University, Houghton, MI 49931, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-3272-6166","authenticated-orcid":false,"given":"Jaden","family":"Schneider","sequence":"additional","affiliation":[{"name":"Department of Biological Science, College of Sciences and Arts, Michigan Technological University, Houghton, MI 49931, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas","family":"Detterman","sequence":"additional","affiliation":[{"name":"Department of Biological Science, College of Sciences and Arts, Michigan Technological University, Houghton, MI 49931, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoyun","family":"Shu","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang 330006, China"},{"name":"Department of Biological Science, College of Sciences and Arts, Michigan Technological University, Houghton, MI 49931, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-5946-6999","authenticated-orcid":false,"given":"Tyler","family":"Gregersen","sequence":"additional","affiliation":[{"name":"Department of Biological Science, College of Sciences and Arts, Michigan Technological University, Houghton, MI 49931, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maximo Nahas","family":"Folch","sequence":"additional","affiliation":[{"name":"Department of Biological Science, College of Sciences and Arts, Michigan Technological University, Houghton, MI 49931, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4108-0989","authenticated-orcid":false,"given":"Yong","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang 330006, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shibiao","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang 330006, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Biological Science, College of Sciences and Arts, Michigan Technological University, Houghton, MI 49931, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2593","DOI":"10.1681\/ASN.2018050493","article-title":"Prevalence Estimates of Polycystic Kidney and Liver Disease by Population Sequencing","volume":"29","author":"Lanktree","year":"2018","journal-title":"J. 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