{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T10:31:51Z","timestamp":1785407511723,"version":"3.56.0"},"reference-count":36,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2026,4,20]],"date-time":"2026-04-20T00:00:00Z","timestamp":1776643200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100008766","name":"Fujian Agriculture and Forestry University","doi-asserted-by":"publisher","award":["22001XA"],"award-info":[{"award-number":["22001XA"]}],"id":[{"id":"10.13039\/501100008766","id-type":"DOI","asserted-by":"publisher"}]},{"award":["22001XA"],"award-info":[{"award-number":["22001XA"]}],"id":[{"id":"https:\/\/ror.org\/04kx2sy84","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Acute kidney injury (AKI) continues to pose a significant clinical challenge due to its high morbidity rates and limited therapeutic options. Recent evidence suggests that natural compounds may provide renoprotective benefits by modulating oxidative stress and inflammation. This study examines the protective effects of a novel polysaccharide peptide extracted from Ganoderma lucidum (GL-PPQ1) against renal ischemia\u2013reperfusion (I\/R) injury, with particular emphasis on the integrin \u03b23\/Fibronectin 1 (Fn1) signaling axis. A murine model of renal I\/R injury was established, and GL-PPQ1 was administered orally for seven days before surgery. The assessment included renal function, histopathology, oxidative stress markers, and inflammatory cytokines. Additionally, transcriptomic profiling and protein expression analyses were conducted to elucidate the underlying mechanisms. The results revealed that GL-PPQ1 pretreatment significantly reduced renal tubular damage, lowered serum creatinine and blood urea nitrogen levels, and diminished oxidative stress and inflammatory responses. RNA sequencing revealed that GL-PPQ1 affected gene sets associated with extracellular matrix remodeling and cell adhesion. Western blot and immunohistochemistry further confirmed that GL-PPQ1 decreased the expression of integrin \u03b23 and Fn1, suggesting a regulatory effect on their interaction during I\/R injury. These findings demonstrate that GL-PPQ1 offers substantial kidney protection by mitigating oxidative stress, inflammation, and dysregulation of the integrin \u03b23\/Fn1 signaling pathway. Thus, this study supports that polysaccharide peptides derived from Ganoderma lucidum could have the potential to serve as both a dietary supplement and a therapeutic agent in the treatment of AKI.<\/jats:p>","DOI":"10.3390\/biom16040610","type":"journal-article","created":{"date-parts":[[2026,4,20]],"date-time":"2026-04-20T13:22:47Z","timestamp":1776691367000},"page":"610","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Polysaccharide Peptide from Ganoderma lucidum Reduces Acute Kidney Injury Through Regulating the Integrin \u03b23\/Fn1 Axis"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-6598-9664","authenticated-orcid":false,"given":"Hatungimana","family":"Mediatrice","sequence":"first","affiliation":[{"name":"National Engineering Research Center of JUNCAO Technology, College of Life Science, Fujian Agriculture and Forestry University, Fuzhou 350002, China"},{"name":"Rwanda Agriculture and Animal Resources Development Board, Kigali P.O. Box 5016, Rwanda"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongjian","family":"Luo","sequence":"additional","affiliation":[{"name":"National Engineering Research Center of JUNCAO Technology, College of Life Science, Fujian Agriculture and Forestry University, Fuzhou 350002, China"},{"name":"Cross-Strait Cooperation Base on Agricultural Science and Technology Industry (Membership) Under the Ministry of Science and Technology (MOST), College of Agriculture, Fujian Agriculture and Forestry University, Fuzhou 350002, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lianfu","family":"Wang","sequence":"additional","affiliation":[{"name":"National Engineering Research Center of JUNCAO Technology, College of Life Science, Fujian Agriculture and Forestry University, Fuzhou 350002, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Yao","sequence":"additional","affiliation":[{"name":"Chongqing Key Laboratory of Development and Utilization of Genuine Medicinal Materials in Three Gorges Reservoir Area, Chongqing 404120, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhujun","family":"Liu","sequence":"additional","affiliation":[{"name":"Chongqing Key Laboratory of Development and Utilization of Genuine Medicinal Materials in Three Gorges Reservoir Area, Chongqing 404120, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-4856-0150","authenticated-orcid":false,"given":"Nsanzinshuti","family":"Aimable","sequence":"additional","affiliation":[{"name":"National Engineering Research Center of JUNCAO Technology, College of Life Science, Fujian Agriculture and Forestry University, Fuzhou 350002, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingping","family":"Hu","sequence":"additional","affiliation":[{"name":"National Engineering Research Center of JUNCAO Technology, College of Life Science, Fujian Agriculture and Forestry University, Fuzhou 350002, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3557-0498","authenticated-orcid":false,"given":"Yukun","family":"Zhang","sequence":"additional","affiliation":[{"name":"Chongqing Key Laboratory of Development and Utilization of Genuine Medicinal Materials in Three Gorges Reservoir Area, Chongqing 404120, China"},{"name":"State Key Laboratory of Natural and Biomimetic Drugs, Department of Pharmacology, School of Basic Medical Sciences, Peking University, Beijing 100191, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhanxi","family":"Lin","sequence":"additional","affiliation":[{"name":"National Engineering Research Center of JUNCAO Technology, College of Life Science, Fujian Agriculture and Forestry University, Fuzhou 350002, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dongmei","family":"Lin","sequence":"additional","affiliation":[{"name":"National Engineering Research Center of JUNCAO Technology, College of Life Science, Fujian Agriculture and Forestry University, Fuzhou 350002, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1391","DOI":"10.1038\/nm.2507","article-title":"Ischemia and reperfusion\u2014From mechanism to translation","volume":"17","author":"Eltzschig","year":"2011","journal-title":"Nat. Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"F684","DOI":"10.1152\/ajprenal.00280.2024","article-title":"Prolonged unilateral renal ischemia-reperfusion as a model for acute to chronic kidney injury in female mice","volume":"328","author":"Stowers","year":"2025","journal-title":"Am. J. Physiol. Ren. Physiol."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Zhang, L., Luo, F., Yuan, N., Yin, J., Shen, B., Chai, Y., Sun, L., Wang, X., Yin, L., and Luo, C. (2025). Research progress of ferroptosis in acute kidney injury. Front. Cell Dev. Biol., 13.","DOI":"10.3389\/fcell.2025.1614156"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Fang, H., Lin, D., Li, X., Wang, L., and Yang, T. (2023). Therapeutic potential of Ganoderma lucidum polysaccharide peptide in Doxorubicin-induced nephropathy: Modulation of renin-angiotensin system and proteinuria. Front. Pharmacol., 14.","DOI":"10.3389\/fphar.2023.1287908"},{"key":"ref_5","first-page":"3366","article-title":"Research progress on pharmacological effects and biosynthesis of main active ingredients of Ganoderma","volume":"56","author":"Luo","year":"2025","journal-title":"Chin. Tradit. Herb. Drugs"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Lin, Z.B., and Yang, B.X. (2019). Ganoderma and Health (Biology, Chemistry and Industry), Springer Press.","DOI":"10.1007\/978-981-13-9867-4"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"127336","DOI":"10.1016\/j.ijbiomac.2023.127336","article-title":"Inhibition of intrarenal PRR-RAS pathway by Ganoderma lucidum polysaccharide peptides in proteinuric nephropathy","volume":"253","author":"Fang","year":"2023","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Xie, J., Lin, D., Li, J., Zhou, T., Lin, S., and Lin, Z. (2023). Effects of Ganoderma lucidum polysaccharide peptide ameliorating cyclophosphamide-induced immune dysfunctions based on metabolomics analysis. Front. Nutr., 10.","DOI":"10.3389\/fnut.2023.1179749"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"138378","DOI":"10.1016\/j.ijbiomac.2024.138378","article-title":"Ganoderma Lucidum polysaccharide peptide (GL-PP2): A potential therapeutic agent against sepsis-induced organ injury by modulating Nrf2\/NF-\u03baB pathways","volume":"285","author":"Yang","year":"2025","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"125370","DOI":"10.1016\/j.ijbiomac.2023.125370","article-title":"Ganoderma lucidum polysaccharide peptides GL-PPSQ2 alleviate intestinal ischemia-reperfusion injury via inhibiting cytotoxic neutrophil extracellular traps","volume":"244","author":"Lin","year":"2023","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"123594","DOI":"10.1016\/j.carbpol.2025.123594","article-title":"A novel galactoglucan from Ganoderma lucidum ameliorates ethanol-induced gastric ulcers by modulating FAK-MAPK signaling pathway","volume":"360","author":"Luo","year":"2025","journal-title":"Carbohydr. Polym."},{"key":"ref_12","first-page":"1619","article-title":"The role of integrins in inflammation and angiogenesis","volume":"89","author":"Maheshwari","year":"2020","journal-title":"Pediatr. Res."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"123838","DOI":"10.1016\/j.carbpol.2025.123838","article-title":"Structural feature and antitumor activity of a N-acetylglucosamine containing polysaccharide from Ganoderma sinense","volume":"366","author":"Feng","year":"2025","journal-title":"Carbohydr. Polym."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1250","DOI":"10.1093\/jpp\/rgab058","article-title":"Ganoderma lucidum ameliorates the diabetic nephropathy via down-regulatory effect on TGF\u03b2-1 and TLR-4\/NF\u03baB signalling pathways","volume":"73","author":"Hassan","year":"2021","journal-title":"J. Pharm. Pharmacol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1007\/978-3-030-80614-9_4","article-title":"Basic components of connective tissues and extracellular matrix: Fibronectin, fibrinogen, laminin, elastin, fibrillins, fibulins, matrilins, tenascins and thrombospondins","volume":"1348","author":"Halper","year":"2021","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"129793","DOI":"10.1016\/j.ijbiomac.2024.129793","article-title":"Structural characterization and anti-oxidative activity for a glycopeptide from Ganoderma lucidum fruiting body","volume":"261","author":"Luo","year":"2024","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"155975","DOI":"10.1016\/j.phymed.2024.155975","article-title":"Ligustilide alleviates oxidative stress during renal ischemia-reperfusion injury through maintaining Sirt3-dependent mitochondrial homeostasis","volume":"134","author":"Xia","year":"2024","journal-title":"Phytomedicine"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Ma, Y., Zabell, T., Creasy, A., Yang, X., Chatterjee, V., Villalba, N., Kistler, E.B., Wu, M.H., and Yuan, S.Y. (2020). Gut Ischemia Reperfusion Injury Induces Lung Inflammation via Mesenteric Lymph-Mediated Neutrophil Activation. Front. Immunol., 11.","DOI":"10.3389\/fimmu.2020.586685"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Wang, J., Zhu, H., Miao, J., Lin, W., and Han, F. (2024). Bilateral renal ischemia-reperfusion model for acute kidney injury in mice. J. Vis. Exp. (JoVE), e65838.","DOI":"10.3791\/65838"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"bio059988","DOI":"10.1242\/bio.059988","article-title":"Quantifying acute kidney injury in an Ischaemia-Reperfusion Injury mouse model using deep-learning-based semantic segmentation in histology","volume":"12","author":"Luchian","year":"2023","journal-title":"Biol. Open"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Lin, Q., Zhao, J., Yin, G., Mei, X., Liu, C., Zhang, X., Zhao, H., Wang, W., Lu, N., and Sun, D. (2025). Ascidians extract ameliorates cisplatin-induced acute kidney injury via relieving cell membrane damage. Food Sci. Hum. Wellness.","DOI":"10.26599\/FSHW.2025.9250767"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Mirzayans, R., and Murray, D. (2020). Do TUNEL and other apoptosis assays detect cell death in preclinical studies?. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21239090"},{"key":"ref_23","unstructured":"Riss, T., Niles, A., Moravec, R., Karassina, N., and Vidugiriene, J. (2019). Cytotoxicity assays: In vitro methods to measure dead cells, Assay Guidance Manual [Internet]."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"338","DOI":"10.1038\/s41419-018-0358-7","article-title":"Ischemic preconditioning attenuates ischemia\/reperfusion-induced kidney injury by activating autophagy via the SGK1 signaling pathway","volume":"9","author":"Xie","year":"2018","journal-title":"Cell Death Dis."},{"key":"ref_25","first-page":"633","article-title":"TRPC6 may protect renal ischemia-reperfusion injury through inhibiting necroptosis of renal tubular epithelial cells","volume":"22","author":"Shen","year":"2016","journal-title":"Med. Sci. Monit. Int. Med. J. Exp. Clin. Res."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"496","DOI":"10.4236\/ijcm.2016.77055","article-title":"Macrophage TGF-\u03b21 and the proapoptotic extracellular matrix protein BIGH3 induce renal cell apoptosis in prediabetic and diabetic conditions","volume":"7","author":"Moritz","year":"2016","journal-title":"Int. J. Clin. Med."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"100696","DOI":"10.1016\/j.xpro.2021.100696","article-title":"ACE2 chromogenic immunostaining protocol optimized for formalin-fixed paraffin-embedded human tissue sections","volume":"2","author":"Jorgensen","year":"2021","journal-title":"STAR Protoc."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1521","DOI":"10.1093\/ckj\/sfad071","article-title":"Kidney injury molecule 1 (KIM-1): A potential biomarker of acute kidney injury and tubulointerstitial injury in patients with ANCA-glomerulonephritis","volume":"16","author":"Brilland","year":"2023","journal-title":"Clin. Kidney J."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"74","DOI":"10.5395\/rde.2014.39.1.74","article-title":"Analysis of variance (ANOVA) comparing means of more than two groups","volume":"39","author":"Kim","year":"2014","journal-title":"Restor. Dent. Endod."},{"key":"ref_30","first-page":"831","article-title":"Morphologic, biochemical, and molecular evidence of apoptosis during the reperfusion phase after brief periods of renal ischemia","volume":"140","author":"Schumer","year":"1992","journal-title":"Am. J. Pathol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"102067","DOI":"10.1016\/j.omtn.2023.102067","article-title":"Alleviation of ischemia-reperfusion induced renal injury by chemically modified SOD2 mRNA delivered via lipid nanoparticles","volume":"34","author":"Hou","year":"2023","journal-title":"Mol. Ther. Nucleic Acids"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"16910","DOI":"10.1038\/srep16910","article-title":"Ganoderma lucidum polysaccharide peptide prevents renal ischemia reperfusion injury via counteracting oxidative stress","volume":"5","author":"Zhong","year":"2015","journal-title":"Sci. Rep."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"e03","DOI":"10.34172\/npj.2021.03","article-title":"Herbal antioxidants and renal ischemic-reperfusion injury;an updated review","volume":"10","author":"Asgharpour","year":"2021","journal-title":"J. Nephropharmacol."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Li, S., Jiang, S., Zhang, Q., Jin, B., Lv, D., Li, W., Zhao, M., Jiang, C., Dai, C., and Liu, Z. (2021). Integrin \u03b23 induction promotes tubular cell senescence and kidney fibrosis. Front. Cell Dev. Biol., 9.","DOI":"10.3389\/fcell.2021.733831"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"e169885","DOI":"10.1172\/jci.insight.169885","article-title":"Integrin \u03b21-rich extracellular vesicles of kidney recruit Fn1+ macrophages to aggravate ischemia-reperfusion-induced inflammation","volume":"9","author":"Wang","year":"2024","journal-title":"JCI Insight"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1038\/s41420-024-01979-4","article-title":"The emerging role of regulated cell death in ischemia and reperfusion-induced acute kidney injury: Current evidence and future perspectives","volume":"10","author":"Li","year":"2024","journal-title":"Cell Death Discov."}],"container-title":["Biomolecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2218-273X\/16\/4\/610\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,25]],"date-time":"2026-04-25T04:13:27Z","timestamp":1777090407000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2218-273X\/16\/4\/610"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,20]]},"references-count":36,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2026,4]]}},"alternative-id":["biom16040610"],"URL":"https:\/\/doi.org\/10.3390\/biom16040610","relation":{},"ISSN":["2218-273X"],"issn-type":[{"value":"2218-273X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,20]]}}}