{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T17:39:40Z","timestamp":1783618780095,"version":"3.55.0"},"reference-count":78,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2025,9,5]],"date-time":"2025-09-05T00:00:00Z","timestamp":1757030400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministry of Science and Technology, Taiwan","award":["111-2314-B-030-005-MY3"],"award-info":[{"award-number":["111-2314-B-030-005-MY3"]}]},{"name":"Ministry of Science and Technology, Taiwan","award":["114-2314-B-030-003"],"award-info":[{"award-number":["114-2314-B-030-003"]}]},{"name":"Ministry of Science and Technology, Taiwan","award":["PL-202508008V"],"award-info":[{"award-number":["PL-202508008V"]}]},{"DOI":"10.13039\/501100013784","name":"Fu Jen Catholic University Hospital","doi-asserted-by":"publisher","award":["111-2314-B-030-005-MY3"],"award-info":[{"award-number":["111-2314-B-030-005-MY3"]}],"id":[{"id":"10.13039\/501100013784","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100013784","name":"Fu Jen Catholic University Hospital","doi-asserted-by":"publisher","award":["114-2314-B-030-003"],"award-info":[{"award-number":["114-2314-B-030-003"]}],"id":[{"id":"10.13039\/501100013784","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100013784","name":"Fu Jen Catholic University Hospital","doi-asserted-by":"publisher","award":["PL-202508008V"],"award-info":[{"award-number":["PL-202508008V"]}],"id":[{"id":"10.13039\/501100013784","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antioxidants"],"abstract":"<jats:p>Hydrogen sulfide (H2S) exerts regulatory functions in kidney diseases. However, its protective role against kidney stone formation remains unclear. Here, we demonstrate that hyperoxaluria or oxalate exposure impairs H2S formation, leading to tubular injury and calcium oxalate (CaOx) crystal deposition in both in vivo and in vitro models. In male rats fed 5% hydroxy-L-proline (HP), time-dependent increases in urinary supersaturation, tubular damage, and renal CaOx deposition were observed compared to controls. These changes were associated with the decreased expression of H2S-producing enzymes and elevated urinary secretion of osteopontin (OPN) and Tamm\u2013Horsfall protein (THP). Notably, the protein level and activity of specificity protein 1 (Sp1), a transcription factor regulating these enzymes, were markedly decreased in HP-treated kidneys. Chronic supplementation with the H2S donor GYY4137 (GYY) significantly attenuated HP-induced tubular injury and CaOx deposition by reducing OPN and THP secretion. Consistent with in vivo results, H2S donors mitigated oxalate-induced tubular cell damage and CaOx formation in MDCK cells. Mechanistically, oxalate activated cyclic AMP\/protein kinase A (PKA) signaling, which promoted OPN and THP secretion; these effects were eradicated by the PKA inhibitor H89 or GYY. These findings indicate that hyperoxaluria impairs Sp1 transcriptional activity, resulting in H2S deficiency and compromised anticrystallization defense in oxalate-induced tubulopathy.<\/jats:p>","DOI":"10.3390\/antiox14091088","type":"journal-article","created":{"date-parts":[[2025,9,5]],"date-time":"2025-09-05T14:53:01Z","timestamp":1757083981000},"page":"1088","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Hydrogen Sulfide Deficiency Contributes to Tubular Damage and Calcium Oxalate Crystal Formation in Hyperoxaluria Nephropathy: Role of Osteopontin and Tamm\u2013Horsfall Protein"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9452-5179","authenticated-orcid":false,"given":"Chien-Lin","family":"Lu","sequence":"first","affiliation":[{"name":"School of Medicine, College of Medicine, Fu Jen Catholic University, New Taipei 242062, Taiwan"},{"name":"Division of Nephrology, Department of Internal Medicine, Fu Jen Catholic University Hospital, Fu Jen Catholic University, New Taipei 243089, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi-Shiou","family":"Tseng","sequence":"additional","affiliation":[{"name":"Division of Urology, Department of Surgery, Far Eastern Memorial Hospital, New Taipei 220216, Taiwan"},{"name":"Department of Chemical Engineering and Materials Science, Yuan Ze University, Taoyuan 320315, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9248-5030","authenticated-orcid":false,"given":"Wen-Bin","family":"Wu","sequence":"additional","affiliation":[{"name":"School of Medicine, College of Medicine, Fu Jen Catholic University, New Taipei 242062, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chun-Hou","family":"Liao","sequence":"additional","affiliation":[{"name":"School of Medicine, College of Medicine, Fu Jen Catholic University, New Taipei 242062, Taiwan"},{"name":"Divisions of Urology, Department of Surgery, Cardinal Tien Hospital, New Taipei 231009, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0040-5203","authenticated-orcid":false,"given":"Ming-Chieh","family":"Ma","sequence":"additional","affiliation":[{"name":"School of Medicine, College of Medicine, Fu Jen Catholic University, New Taipei 242062, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,9,5]]},"reference":[{"key":"ref_1","first-page":"14","article-title":"Hyperoxaluria\u2014A Major Metabolic Risk for Kidney Stone Disease","volume":"106","author":"Owino","year":"2023","journal-title":"Rhode Isl. 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