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Hu antigen R (HuR) is recognized as a crucial modulator in inflammation. We hypothesized that elevated HuR contributes to the transition from septic AKI to CKD by promoting persistent inflammation and fibrosis, and inhibition of HuR may reverse septic kidney injury. Mice subjected to lipopolysaccharide (LPS) injections every other day were concurrently treated without or with either KH39 or niclosamide (NCS) for 7 days. Control mice received saline injections. Repeated LPS injections led to a significant increase in HuR expression in the kidneys, which was effectively suppressed by KH39 or NCS treatment. LPS-induced kidney injury was characterized by elevated plasma blood urea nitrogen levels and urinary albuminuria, along with histological signs of inflammatory cell infiltration and fibrosis, as determined by periodic acid\u2013Schiff and Masson\u2019s trichrome staining, and immunofluorescent staining for markers such as \u03b1-smooth muscle actin, fibronectin, collagen III, and F4\/80. Treatment with either KH39 or NCS mitigated these changes observed in LPS-injured kidneys. Additionally, increased expression of CD147, a molecule implicated in inflammatory cell recruitment and tubular injury, was inhibited by KH39 or NCS treatment. These effects on HuR and CD147 expression were further validated in vitro in cultured macrophages and tubular cells. This study suggests that HuR elevation in LPS-stimulated macrophages and kidney cells contributes to the progression of septic kidney injury, possibly through HuR-CD147 interactions, underscoring the therapeutic potential of HuR inhibitors for this condition.<\/jats:p>","DOI":"10.1042\/cs20241756","type":"journal-article","created":{"date-parts":[[2024,12,24]],"date-time":"2024-12-24T06:18:46Z","timestamp":1735021126000},"page":"69-84","update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["RNA-binding protein HuR regulates the transition of septic AKI to CKD by modulating CD147"],"prefix":"10.1042","volume":"139","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1815-8087","authenticated-orcid":false,"given":"Simeng","family":"Liu","sequence":"first","affiliation":[{"name":"1Division of Nephrology & Hypertension, Department of Internal Medicine, University of Utah Health Science, Salt Lake City, UT, USA"},{"name":"2Division of Nephrology, Department of Internal Medicine, Nanjing Medical University Jiangsu Province Hospital, Nanjing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renfei","family":"Luo","sequence":"additional","affiliation":[{"name":"1Division of Nephrology & Hypertension, Department of Internal Medicine, University of Utah Health Science, Salt Lake City, UT, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Davey","family":"Li","sequence":"additional","affiliation":[{"name":"1Division of Nephrology & Hypertension, Department of Internal Medicine, University of Utah Health Science, Salt Lake City, UT, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Tang","sequence":"additional","affiliation":[{"name":"1Division of Nephrology & Hypertension, Department of Internal Medicine, University of Utah Health Science, Salt Lake City, UT, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuli","family":"Qiu","sequence":"additional","affiliation":[{"name":"2Division of Nephrology, Department of Internal Medicine, Nanjing Medical University Jiangsu Province Hospital, Nanjing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryan P.","family":"Sherrier","sequence":"additional","affiliation":[{"name":"3Department of Chemistry, Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey","family":"Aube","sequence":"additional","affiliation":[{"name":"3Department of Chemistry, Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC, USA"},{"name":"4Department of Chemical Biology and Medical Chemistry, Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoqing","family":"Wu","sequence":"additional","affiliation":[{"name":"5Department of Molecular Biosciences, University of Kansas, Lawrence, KS, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liang","family":"Xu","sequence":"additional","affiliation":[{"name":"5Department of Molecular Biosciences, University of Kansas, Lawrence, KS, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9186-5269","authenticated-orcid":false,"given":"Yufeng","family":"Huang","sequence":"additional","affiliation":[{"name":"1Division of Nephrology & Hypertension, Department of Internal Medicine, University of Utah Health Science, Salt Lake City, UT, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"288","published-online":{"date-parts":[[2025,1,15]]},"reference":[{"key":"2025011706414039800_CS-2024-1756C1","doi-asserted-by":"crossref","first-page":"1083","DOI":"10.1016\/j.kint.2019.05.026","article-title":"Acute kidney injury from sepsis: current concepts, epidemiology, pathophysiology, prevention and treatment","volume":"96","author":"Peerapornratana","year":"2019","journal-title":"Kidney Int."},{"key":"2025011706414039800_CS-2024-1756C2","doi-asserted-by":"crossref","first-page":"1050","DOI":"10.2215\/CJN.00850122","article-title":"The pathophysiology of sepsis-associated AKI","volume":"17","author":"Kuwabara","year":"2022","journal-title":"Clin. 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