{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T11:09:27Z","timestamp":1785409767004,"version":"3.56.0"},"reference-count":50,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2026,6,25]],"date-time":"2026-06-25T00:00:00Z","timestamp":1782345600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["RS-2025-00517056"],"award-info":[{"award-number":["RS-2025-00517056"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["RS-2025-02214748"],"award-info":[{"award-number":["RS-2025-02214748"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"award":["RS-2025-00517056"],"award-info":[{"award-number":["RS-2025-00517056"]}],"id":[{"id":"https:\/\/ror.org\/013aysd81","id-type":"ROR","asserted-by":"publisher"}]},{"award":["RS-2025-02214748"],"award-info":[{"award-number":["RS-2025-02214748"]}],"id":[{"id":"https:\/\/ror.org\/013aysd81","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biology"],"abstract":"<jats:p>Background: The kidney is an organ rich in peroxisomes, which play a pivotal role in fatty acid oxidation and ROS decomposition. Importantly, peroxisomal dysfunction contributes to the development and progression of various renal diseases. Therefore, we aimed to elucidate whether peroxisomes affect renal damage and fibrosis over time using a unilateral ureteral obstruction (UUO) mouse model. Methods: Expression levels of peroxisome-related factors and ROS- and hypoxia-related genes in UUO mice were measured in a time-dependent manner. Results: UUO led to renal damage and fibrosis progression over time; it significantly increased the protein expression levels of ATG5 and ATG7, while it decreased PMP70 and PEX14 protein expression. In particular, UUO increased the protein expression level of pexophagy receptor NBR1. Although the number of peroxisomes decreased, the protein expression levels of peroxisomal biogenesis-related proteins such as PEX11b, PEX16, and PEX19 remained constant. Decreased lipid metabolism due to reductions in ACOX1, DBP, and catalase caused by UUO and increased ROS production through peroxisomal degradation and mitochondrial antioxidant enzyme dysfunction were observed. Additionally, HIF-1\u03b1 protein levels gradually increased in the UUO mice, whereas those of HIF-2\u03b1 initially increased and then decreased. Conclusions: UUO is characterized by a progressive, chronological reduction in peroxisomal markers. Our findings indicate that peroxisomal degradation and associated metabolic dysfunction are tightly correlated with the progression of kidney injury and fibrosis, suggesting a potential involvement of compromised peroxisomal homeostasis in renal pathogenesis rather than proving a direct causal mechanism. Maintaining peroxisomal quality control may nevertheless represent a potential therapeutic avenue for chronic kidney disease.<\/jats:p>","DOI":"10.3390\/biology15130996","type":"journal-article","created":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T16:50:33Z","timestamp":1782924633000},"page":"996","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Peroxisomal Degradation Correlates with the Progression of Kidney Injury in a UUO Mouse Model"],"prefix":"10.3390","volume":"15","author":[{"given":"Jinhwi","family":"Kim","sequence":"first","affiliation":[{"name":"Department of Biomedical Science and Engineering, Gwangju Institute of Science and Technology, Gwangju 61005, Republic of Korea"},{"name":"Department of Colorectal Surgery, Wonkwang University Hospital, Iksan 54538, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyunsoo","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Biomedical Science and Engineering, Gwangju Institute of Science and Technology, Gwangju 61005, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-8992-421X","authenticated-orcid":false,"given":"Arun","family":"Chhetri","sequence":"additional","affiliation":[{"name":"Department of Biomedical Science and Engineering, Gwangju Institute of Science and Technology, Gwangju 61005, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-3759-6388","authenticated-orcid":false,"given":"Laxman","family":"Manandhar","sequence":"additional","affiliation":[{"name":"Department of Biomedical Science and Engineering, Gwangju Institute of Science and Technology, Gwangju 61005, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gyuho","family":"Jang","sequence":"additional","affiliation":[{"name":"Department of Biomedical Science and Engineering, Gwangju Institute of Science and Technology, Gwangju 61005, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-5994-7004","authenticated-orcid":false,"given":"Channy","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Biomedical Science and Engineering, Gwangju Institute of Science and Technology, Gwangju 61005, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1146-599X","authenticated-orcid":false,"given":"Raekil","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Biomedical Science and Engineering, Gwangju Institute of Science and Technology, Gwangju 61005, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1089\/ars.2016.6666","article-title":"Peroxisomes and Kidney Injury","volume":"25","author":"Vasko","year":"2016","journal-title":"Antioxid. Redox Signal"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"987","DOI":"10.1016\/j.kint.2022.01.029","article-title":"Nuclear farnesoid X receptor attenuates acute kidney injury through fatty acid oxidation","volume":"101","author":"Xu","year":"2022","journal-title":"Kidney Int."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"156173","DOI":"10.1016\/j.metabol.2025.156173","article-title":"Role of peroxisomes in the pathogenesis and therapy of renal fibrosis","volume":"166","author":"Zhang","year":"2025","journal-title":"Metabolism"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1186\/s12935-017-0451-5","article-title":"The role of ppar\u03b3 and autophagy in ros production, lipid droplets biogenesis and its involvement with colorectal cancer cells modulation","volume":"17","year":"2017","journal-title":"Cancer Cell Int."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Huang, J., Liang, Y., and Zhou, L. (2023). Natural products for kidney disease treatment: Focus on targeting mitochondrial dysfunction. Front. Pharmacol., 14.","DOI":"10.3389\/fphar.2023.1142001"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"867","DOI":"10.1038\/ki.2008.350","article-title":"Chronic hypoxia as a mechanism of progression of chronic kidney diseases: From hypothesis to novel therapeutics","volume":"74","author":"Fine","year":"2008","journal-title":"Kidney Int."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1248","DOI":"10.1111\/jcmm.13060","article-title":"Signalling pathways involved in hypoxia-induced renal fibrosis","volume":"21","author":"Liu","year":"2017","journal-title":"J. Cell. Mol. Med."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1277","DOI":"10.1097\/01.ASN.0000125614.35046.10","article-title":"Evidence of tubular hypoxia in the early phase in the remnant kidney model","volume":"15","author":"Manotham","year":"2004","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1038\/s41420-021-00443-x","article-title":"SIRT1 attenuates renal fibrosis by repressing HIF-2\u03b1","volume":"7","author":"Li","year":"2021","journal-title":"Cell Death Discov."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1007\/978-1-0716-1382-5_22","article-title":"Mouse Models of Kidney Fibrosis","volume":"2299","author":"Kramann","year":"2021","journal-title":"Methods Mol. Biol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1186\/s12964-024-01862-w","article-title":"Peroxisomal homeostasis in metabolic diseases and its implication in ferroptosis","volume":"22","author":"Han","year":"2024","journal-title":"Cell Commun. Signal."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1486","DOI":"10.1038\/s12276-020-00503-9","article-title":"Peroxisome quality control and dysregulated lipid metabolism in neurodegenerative diseases","volume":"52","author":"Jo","year":"2020","journal-title":"Exp. Mol. Med."},{"key":"ref_13","first-page":"939","article-title":"NBR1 acts as an autophagy receptor for peroxisomes","volume":"126","author":"Deosaran","year":"2013","journal-title":"J. Cell Sci."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Wei, X., Manandhar, L., Kim, H., Chhetri, A., Hwang, J., Jang, G., Park, C., and Park, R. (2025). Pexophagy and Oxidative Stress: Focus on Peroxisomal Proteins and Reactive Oxygen Species (ROS) Signaling Pathways. Antioxidants, 14.","DOI":"10.3390\/antiox14020126"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Miguel, V., Titua\u00f1a, J., Herrero, J.I., Herrero, L., Serra, D., Cuevas, P., Barbas, C., Puyol, D.R., M\u00e1rquez-Exp\u00f3sito, L., and Ruiz-Ortega, M. (2021). Renal tubule Cpt1a overexpression protects from kidney fibrosis by restoring mitochondrial homeostasis. J. Clin. Investig., 131.","DOI":"10.1172\/JCI140695"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1177\/0023677220909401","article-title":"Refining the unilateral ureteral obstruction mouse model: No sham, no shame","volume":"55","author":"Atkinson","year":"2021","journal-title":"Lab. Anim."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Chen, T., Zhang, Z., and Lai, C. (2025). Improvement of the reversible unilateral ureteral obstruction model. Ren. Fail., 47.","DOI":"10.1080\/0886022X.2025.2454721"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"102080","DOI":"10.1016\/j.molmet.2024.102080","article-title":"TMEM135 deficiency improves hepatic steatosis by suppressing CD36 in a SIRT1-dependent manner","volume":"92","author":"Chhetri","year":"2025","journal-title":"Mol. Metab."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1038\/s12276-025-01396-2","article-title":"Golgi condensation causes intestinal lipid accumulation through HIF-1\u03b1-mediated GM130 ubiquitination by NEDD4","volume":"57","author":"Kim","year":"2025","journal-title":"Exp. Mol. Med."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"12780","DOI":"10.18632\/aging.202947","article-title":"CircRNA_30032 promotes renal fibrosis in UUO model mice via miRNA-96-5p\/HBEGF\/KRAS axis","volume":"13","author":"Yi","year":"2021","journal-title":"Aging"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1186\/s12964-024-01524-x","article-title":"TFEB activation triggers pexophagy for functional adaptation during oxidative stress under calcium deficient-conditions","volume":"22","author":"Manandhar","year":"2024","journal-title":"Cell Commun. Signal."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Wei, X., Maharjan, Y., Dorotea, D., Dutta, R.K., Kim, D., Kim, H., Mu, Y., Park, C., and Park, R. (2021). Knockdown of PEX16 Induces Autophagic Degradation of Peroxisomes. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22157989"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1145","DOI":"10.1038\/ki.2009.86","article-title":"Ureteral obstruction as a model of renal interstitial fibrosis and obstructive nephropathy","volume":"75","author":"Chevalier","year":"2009","journal-title":"Kidney Int."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Washino, S., Hosohata, K., and Miyagawa, T. (2020). Roles Played by Biomarkers of Kidney Injury in Patients with Upper Urinary Tract Obstruction. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21155490"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"984","DOI":"10.1016\/j.bbamcr.2015.09.032","article-title":"Peroxisome homeostasis: Mechanisms of division and selective degradation of peroxisomes in mammals","volume":"1863","author":"Honsho","year":"2016","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Brites, P., Ferreira, A.S., da Silva, T.F., Sousa, V.F., Malheiro, A.R., Duran, M., Waterham, H.R., Baes, M., and Wanders, R.J. (2011). Alkyl-glycerol rescues plasmalogen levels and pathology of ether-phospholipid deficient mice. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0028539"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1016\/S0022-2275(20)38538-2","article-title":"Plasmalogen biosynthesis in peroxisomal disorders: Fatty alcohol versus alkylglycerol precursors","volume":"29","author":"Schrakamp","year":"1988","journal-title":"J. Lipid Res."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1038\/s41419-022-04856-z","article-title":"Proximal tubular RAGE mediated the renal fibrosis in UUO model mice via upregulation of autophagy","volume":"13","author":"Liu","year":"2022","journal-title":"Cell Death Dis."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1028","DOI":"10.1016\/j.bbadis.2012.11.021","article-title":"Oxidative stress and pulmonary fibrosis","volume":"1832","author":"Cheresh","year":"2013","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Mart\u00ednez-Klimova, E., Aparicio-Trejo, O.E., Tapia, E., and Pedraza-Chaverri, J. (2019). Unilateral Ureteral Obstruction as a Model to Investigate Fibrosis-Attenuating Treatments. Biomolecules, 9.","DOI":"10.3390\/biom9040141"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"5348","DOI":"10.7150\/thno.87416","article-title":"Tet1 deficiency exacerbates oxidative stress in acute kidney injury by regulating superoxide dismutase","volume":"13","author":"Fan","year":"2023","journal-title":"Theranostics"},{"key":"ref_32","first-page":"4574","article-title":"T-type calcium channel blocker attenuates unilateral ureteral obstruction-induced renal interstitial fibrosis by activating the Nrf2 antioxidant pathway","volume":"8","author":"Chung","year":"2016","journal-title":"Am. J. Transl. Res."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Frange\u017e, \u017d., G\u00e9rard, D., He, Z., Gavriil, M., Fern\u00e1ndez-Marrero, Y., Seyed Jafari, S.M., Hunger, R.E., Lucarelli, P., Yousefi, S., and Sauter, T. (2021). ATG5 and ATG7 Expression Levels Are Reduced in Cutaneous Melanoma and Regulated by NRF1. Front. Oncol., 11.","DOI":"10.3389\/fonc.2021.721624"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1331","DOI":"10.1038\/ki.2010.550","article-title":"Lower estimated glomerular filtration rate and higher albuminuria are associated with mortality and end-stage renal disease. A collaborative meta-analysis of kidney disease population cohorts","volume":"79","author":"Astor","year":"2011","journal-title":"Kidney Int."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"325","DOI":"10.5607\/en.2015.24.4.325","article-title":"The Role of Oxidative Stress in Neurodegenerative Diseases","volume":"24","author":"Kim","year":"2015","journal-title":"Exp. Neurobiol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"585","DOI":"10.1007\/978-981-13-8871-2_29","article-title":"Oxidative Stress and Renal Fibrosis: Mechanisms and Therapies","volume":"1165","author":"Su","year":"2019","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"589","DOI":"10.1016\/j.neuron.2020.02.021","article-title":"Loss- or Gain-of-Function Mutations in ACOX1 Cause Axonal Loss via Different Mechanisms","volume":"106","author":"Chung","year":"2020","journal-title":"Neuron"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"261","DOI":"10.32604\/biocell.2023.024738","article-title":"Hypoxia-induced reactive oxygen species in organ and tissue fibrosis","volume":"47","author":"Xie","year":"2022","journal-title":"Biocell"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"C935","DOI":"10.1152\/ajpcell.00458.2023","article-title":"HIF-1 contributes to autophagy activation via BNIP3 to facilitate renal fibrosis in hypoxia in vitro and UUO in vivo","volume":"326","author":"Liu","year":"2024","journal-title":"Am. J. Physiol. Cell Physiol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"602","DOI":"10.1016\/j.cyto.2012.10.024","article-title":"Associations of vascular endothelial growth factor (VEGF) with adhesion and inflammation molecules in a healthy population","volume":"61","author":"Stathopoulou","year":"2013","journal-title":"Cytokine"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"24204","DOI":"10.1074\/jbc.M109.006510","article-title":"Hypoxia-induced expression of carbonic anhydrase 9 is dependent on the unfolded protein response","volume":"284","author":"Koritzinsky","year":"2009","journal-title":"J. Biol. Chem."},{"key":"ref_42","first-page":"55","article-title":"Pexophagy: Molecular Mechanisms and Implications for Health and Diseases","volume":"41","author":"Cho","year":"2018","journal-title":"Mol. Cells"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"112037","DOI":"10.1016\/j.celrep.2023.112037","article-title":"The selective autophagy adaptor p62\/SQSTM1 forms phase condensates regulated by HSP27 that facilitate the clearance of damaged lysosomes via lysophagy","volume":"42","author":"Gallagher","year":"2023","journal-title":"Cell Rep."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1038\/s41467-023-44005-4","article-title":"Upregulated pexophagy limits the capacity of selective autophagy","volume":"15","author":"Germain","year":"2024","journal-title":"Nat. Commun."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"127236","DOI":"10.1016\/j.micres.2022.127236","article-title":"The Pex3-mediated peroxisome biogenesis plays a critical role in metabolic biosynthesis, stress response, and pathogenicity in Alternaria alternata","volume":"266","author":"Choo","year":"2023","journal-title":"Microbiol. Res."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1639","DOI":"10.1016\/j.bbamcr.2006.09.030","article-title":"Import of peroxisomal membrane proteins: The interplay of Pex3p- and Pex19p-mediated interactions","volume":"1763","author":"Fujiki","year":"2006","journal-title":"Biochim. Biophys. Acta (BBA)-Mol. Cell Res."},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Farr\u00e9, J.C., Mahalingam, S.S., Proietto, M., and Subramani, S. (2019). Peroxisome biogenesis, membrane contact sites, and quality control. EMBO Rep., 20.","DOI":"10.15252\/embr.201846864"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"976","DOI":"10.1080\/15548627.2016.1166317","article-title":"Persistent activation of autophagy in kidney tubular cells promotes renal interstitial fibrosis during unilateral ureteral obstruction","volume":"12","author":"Livingston","year":"2016","journal-title":"Autophagy"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"13045","DOI":"10.1074\/jbc.M109.067728","article-title":"Kidney-specific overexpression of Sirt1 protects against acute kidney injury by retaining peroxisome function","volume":"285","author":"Hasegawa","year":"2010","journal-title":"J. Biol. Chem."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"442","DOI":"10.4161\/auto.23344","article-title":"Dysfunctional lysosomal autophagy leads to peroxisomal oxidative burnout and damage during endotoxin-induced stress","volume":"9","author":"Vasko","year":"2013","journal-title":"Autophagy"}],"container-title":["Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2079-7737\/15\/13\/996\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T17:56:05Z","timestamp":1782928565000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2079-7737\/15\/13\/996"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,25]]},"references-count":50,"journal-issue":{"issue":"13","published-online":{"date-parts":[[2026,7]]}},"alternative-id":["biology15130996"],"URL":"https:\/\/doi.org\/10.3390\/biology15130996","relation":{},"ISSN":["2079-7737"],"issn-type":[{"value":"2079-7737","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,25]]}}}