{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T15:35:14Z","timestamp":1783524914240,"version":"3.55.0"},"reference-count":47,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,7,26]],"date-time":"2021-07-26T00:00:00Z","timestamp":1627257600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100010270","name":"Capital Health Research and Development of Special Fund","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100010270","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:p>Modified Huangqi Chifeng decoction (MHCD) has been used to reduce proteinuria in immunoglobulin A nephropathy (IgAN) for many years. Previously, we have demonstrated its protective role in glomerular mesangial cells. Podocyte injury, another key factor associated with proteinuria in IgAN, has also attracted increasing attention. However, whether MHCD can reduce proteinuria by protecting podocytes remains unclear. The present study aimed to investigate the protective effects of MHCD against podocyte injury in a rat model of IgAN. To establish the IgAN model, rats were administered bovine serum albumin, carbon tetrachloride, and lipopolysaccharide. MHCD in three doses or telmisartan was administered once daily for 8 weeks (<jats:italic>n<\/jats:italic> = 10 rats\/group). Rats with IgAN developed proteinuria at week 6, which worsened over time until drug intervention. After drug intervention, MHCD reduced proteinuria and had no effect on liver and kidney function. Furthermore, MHCD alleviated renal pathological lesions, hyperplasia of mesangial cells, mesangial matrix expansion, and podocyte foot process fusion. Western blot analysis revealed that MHCD increased the expression of the podocyte-associated proteins nephrin and podocalyxin. Additionally, we stained podocyte nuclei with an antibody for Wilms\u2019 tumor protein one and found that MHCD increased the podocyte number in rats with IgAN. In conclusion, these results demonstrate that MHCD attenuates proteinuria by reducing podocyte injury.<\/jats:p>","DOI":"10.3389\/fphar.2021.714584","type":"journal-article","created":{"date-parts":[[2021,7,26]],"date-time":"2021-07-26T08:14:42Z","timestamp":1627287282000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":15,"title":["Modified Huangqi Chifeng Decoction Attenuates Proteinuria by Reducing Podocyte Injury in a Rat Model of Immunoglobulin a Nephropathy"],"prefix":"10.3389","volume":"12","author":[{"given":"Meiying","family":"Chang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bin","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liusheng","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuan","family":"Si","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingming","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Hao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinning","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,7,26]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"927","DOI":"10.2217\/bmm-2018-0152","article-title":"Urine Markers of Podocyte Dysfunction: a Review of Podocalyxin and Nephrin in Selected Glomerular Diseases","volume":"12","author":"Akankwasa","year":"2018","journal-title":"Biomarkers Med."},{"key":"B2","doi-asserted-by":"publisher","first-page":"255","DOI":"10.1007\/s10157-003-0259-6","article-title":"The Role of Podocytes in Glomerular Pathobiology","volume":"7","author":"Asanuma","year":"2003","journal-title":"Clin. Exp. Nephrol."},{"key":"B3","doi-asserted-by":"publisher","first-page":"1385","DOI":"10.2215\/CJN.08110811","article-title":"Relationships between Levels of Urinary Podocalyxin, Number of Urinary Podocytes, and Histologic Injury in Adult Patients with IgA Nephropathy","volume":"7","author":"Asao","year":"2012","journal-title":"Clin. J. Am. Soc. Nephrol."},{"key":"B4","doi-asserted-by":"publisher","first-page":"313","DOI":"10.1016\/j.intimp.2019.02.056","article-title":"Immunosuppressive Effect of Artemisinin and Hydroxychloroquine Combination Therapy on IgA Nephropathy via Regulating the Differentiation of CD4+ T Cell Subsets in Rats","volume":"70","author":"Bai","year":"","journal-title":"Int. Immunopharmacol."},{"key":"B5","doi-asserted-by":"publisher","first-page":"113619","DOI":"10.1016\/j.bcp.2019.08.021","article-title":"Renoprotective Effects of Artemisinin and Hydroxychloroquine Combination Therapy on IgA Nephropathy via Suppressing NF-\u03baB Signaling and NLRP3 Inflammasome Activation by Exosomes in Rats","volume":"169","author":"Bai","year":"","journal-title":"Biochem. Pharmacol."},{"key":"B6","doi-asserted-by":"publisher","first-page":"403","DOI":"10.1053\/j.ajkd.2013.06.002","article-title":"KDOQI US Commentary on the 2012 KDIGO Clinical Practice Guideline for Glomerulonephritis","volume":"62","author":"Beck","year":"2013","journal-title":"Am. J. Kidney Dis."},{"key":"B7","doi-asserted-by":"publisher","first-page":"310","DOI":"10.1038\/nrneph.2013.72","article-title":"Podocyturia Predicts Pre-eclampsia","volume":"9","author":"Carney","year":"2013","journal-title":"Nat. Rev. Nephrol."},{"key":"B8","doi-asserted-by":"publisher","first-page":"56","DOI":"10.1016\/j.cbi.2017.05.025","article-title":"Role of RAS\/Wnt\/\u03b2-catenin axis Activation in the Pathogenesis of Podocyte Injury and Tubulo-Interstitial Nephropathy","volume":"273","author":"Chen","year":"2017","journal-title":"Chem. Biol. Interact."},{"key":"B9","doi-asserted-by":"publisher","first-page":"339","DOI":"10.1007\/s40620-016-0360-z","article-title":"Clinical and Histological Risk Factors for Progression of IgA Nephropathy: an Update in Children, Young and Adult Patients","volume":"30","author":"Coppo","year":"2017","journal-title":"J. Nephrol."},{"key":"B10","doi-asserted-by":"publisher","first-page":"1832","DOI":"10.1093\/ndt\/gfy338","article-title":"Towards a Personalized Treatment for IgA Nephropathy Considering Pathology and Pathogenesis","volume":"34","author":"Coppo","year":"2019","journal-title":"Nephrol. Dial. Transpl."},{"key":"B11","doi-asserted-by":"publisher","first-page":"104","DOI":"10.1080\/0886022x.2019.1583113","article-title":"Hirudin Ameliorates Immunoglobulin A Nephropathy by Inhibition of Fibrosis and Inflammatory Response","volume":"41","author":"Deng","year":"2019","journal-title":"Ren. Fail."},{"key":"B12","doi-asserted-by":"publisher","first-page":"79","DOI":"10.1016\/j.mvr.2013.04.006","article-title":"Telmisartan Inhibits AGE-Induced Podocyte Damage and Detachment","volume":"88","author":"Fukami","year":"2013","journal-title":"Microvasc. Res."},{"key":"B13","doi-asserted-by":"publisher","first-page":"1486","DOI":"10.7661\/CJIM.2016.12.1486","article-title":"Anti-renal Fibrosis Mechanism of Modified Huangqi Chifeng Decoction Based on TGF-p1\/Smad Signal Pathway","volume":"36","author":"Gao","year":"2016","journal-title":"Zhongguo Zhong Xi Yi Jie He Za Zhi"},{"key":"B14","doi-asserted-by":"publisher","first-page":"451","DOI":"10.1152\/physrev.00055.2006","article-title":"Properties of the Glomerular Barrier and Mechanisms of Proteinuria","volume":"88","author":"Haraldsson","year":"2008","journal-title":"Physiol. Rev."},{"key":"B15","doi-asserted-by":"publisher","first-page":"99","DOI":"10.1159\/000054214","article-title":"Podocyte Injury Predicts Prognosis in Patients with Iga Nephropathy Using a Small Amount of Renal Biopsy Tissue","volume":"24","author":"Hishiki","year":"2001","journal-title":"Kidney Blood Press. Res."},{"key":"B16","doi-asserted-by":"publisher","first-page":"821","DOI":"10.3109\/0886022X.2011.643352","article-title":"Evaluation of Renal Clinicopathological Changes in IgA Nephropathy by Urinary Podocytes Excretion and Podocalyxin Expression","volume":"34","author":"Jiang","year":"2012","journal-title":"Ren. Fail."},{"key":"B17","first-page":"95","article-title":"Single Case Randomized Controlled Research of Modified Huangqi Chifeng Decoction in the Treatment of Proteinuria Due to IgA Nephropathy","volume":"1","author":"Jiao","year":"2018","journal-title":"China Med. Herald"},{"key":"B18","doi-asserted-by":"publisher","first-page":"941","DOI":"10.13935\/j.cnki.sjzx.160715","article-title":"Impacts of the Modified Huangqi Chifeng Decoction on the Proliferation of Glomerular Mesangial Cell and the Secretion of Extracellular Matrix in Mice","volume":"11","author":"Jiao","year":"2016","journal-title":"World J. Integrated Traditional West. Med."},{"key":"B19","doi-asserted-by":"publisher","first-page":"F333","DOI":"10.1152\/ajprenal.00478.2012","article-title":"The Podocyte's Response to Stress: the enigma of Foot Process Effacement","volume":"304","author":"Kriz","year":"2013","journal-title":"Am. J. Physiol. Renal Physiol."},{"key":"B20","doi-asserted-by":"publisher","first-page":"1475","DOI":"10.1046\/j.1523-1755.2002.00269.x","article-title":"Podocytopenia and Disease Severity in IgA Nephropathy","volume":"61","author":"Lemley","year":"2002","journal-title":"Kidney Int."},{"key":"B21","doi-asserted-by":"publisher","first-page":"485","DOI":"10.1016\/j.semnephrol.2018.05.018","article-title":"Role of Mesangial-Podocytic-Tubular Cross-Talk in IgA Nephropathy","volume":"38","author":"Leung","year":"2018","journal-title":"Semin. Nephrol."},{"key":"B22","doi-asserted-by":"publisher","first-page":"1080","DOI":"10.3389\/fphar.2020.01080","article-title":"Zhen-Wu-Tang Protects IgA Nephropathy in Rats by Regulating Exosomes to Inhibit NF-\u03baB\/NLRP3 Pathway","volume":"11","author":"Li","year":"","journal-title":"Front. Pharmacol."},{"key":"B23","doi-asserted-by":"publisher","first-page":"1521","DOI":"10.1016\/j.sjbs.2020.04.034","article-title":"Expression of miRNA-223 and NLRP3 Gene in IgA Patients and Intervention of Traditional Chinese Medicine","volume":"27","author":"Li","year":"","journal-title":"Saudi J. Biol. Sci."},{"key":"B24","doi-asserted-by":"publisher","first-page":"170","DOI":"10.1186\/s13063-016-1774-6","article-title":"Abelmoschus Manihot - a Traditional Chinese Medicine versus Losartan Potassium for Treating IgA Nephropathy: Study Protocol for a Randomized Controlled Trial","volume":"18","author":"Li","year":"2017","journal-title":"Trials"},{"key":"B25","doi-asserted-by":"publisher","first-page":"153231","DOI":"10.1016\/j.phymed.2020.153231","article-title":"Efficacy and Safety of Abelmoschus Manihot for IgA Nephropathy: A Multicenter Randomized Clinical Trial","volume":"76","author":"Li","year":"","journal-title":"Phytomedicine"},{"key":"B26","doi-asserted-by":"publisher","first-page":"31","DOI":"10.1186\/s13063-019-3989-9","article-title":"Treatment Effects of Chinese Medicine (Yi-Qi-Qing-Jie Herbal Compound) Combined with Immunosuppression Therapies in IgA Nephropathy Patients with High-Risk of End-Stage Renal Disease (TCM-WINE): Study Protocol for a Randomized Controlled Trial","volume":"21","author":"Li","year":"2020","journal-title":"Trials"},{"key":"B27","doi-asserted-by":"publisher","first-page":"635","DOI":"10.1016\/j.biopha.2018.02.127","article-title":"Zhen-Wu-tang Protects against Podocyte Injury in Rats with IgA Nephropathy via PPAR\u03b3\/NF-\u03baB Pathway","volume":"101","author":"Liu","year":"2018","journal-title":"Biomed. Pharmacother."},{"key":"B28","doi-asserted-by":"publisher","first-page":"592","DOI":"10.7661\/CJIM.2016.05.0592","article-title":"Effect of Modified Hangqi Chifeng Decoction Containing Serum on the Expression of Col IV, MMP-2, and TIMP-2 in Glomerular Mesangial Cells Induced by LPS","volume":"36","author":"Liu","year":"2016","journal-title":"Zhongguo Zhong Xi Yi Jie He Za Zhi"},{"key":"B29","doi-asserted-by":"publisher","first-page":"35","DOI":"10.33549\/physiolres.932380","article-title":"Temporal and Spatial Expression of Podocyte-Associated Molecules Are Accompanied by Proteinuria in IgA Nephropathy Rat Model","volume":"62","author":"Lu","year":"2013","journal-title":"Physiol. Res."},{"key":"B30","doi-asserted-by":"publisher","first-page":"432","DOI":"10.1001\/jama.2017.9362","article-title":"Effect of Oral Methylprednisolone on Clinical Outcomes in Patients with IgA Nephropathy","volume":"318","author":"Lv","year":"2017","journal-title":"JAMA"},{"key":"B31","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1159\/000348461","article-title":"Role of Podocyte Injury in IgA Nephropathy","volume":"181","author":"Menon","year":"2013","journal-title":"Contrib. Nephrol."},{"key":"B32","doi-asserted-by":"publisher","first-page":"3005","DOI":"10.1097\/01.asn.0000039661.06947.fd","article-title":"Podocyte Biology and Response to Injury","volume":"13","author":"Mundel","year":"2002","journal-title":"J. Am. Soc. Nephrol."},{"key":"B33","doi-asserted-by":"publisher","first-page":"1221","DOI":"10.1016\/j.kint.2016.01.012","article-title":"Podocyte Injury and its Consequences","volume":"89","author":"Nagata","year":"2016","journal-title":"Kidney Int."},{"key":"B34","doi-asserted-by":"publisher","first-page":"429","DOI":"10.1001\/jama.2017.9359","article-title":"Corticosteroids for IgA Nephropathy: TESTING for Benefit, Discovering Harm","volume":"318","author":"O'Shaughnessy","year":"2017","journal-title":"JAMA"},{"key":"B35","doi-asserted-by":"publisher","first-page":"4137","DOI":"10.3748\/wjg.v19.i26.4137","article-title":"Effects of Rhein on Intestinal Epithelial Tight junction in IgA Nephropathy","volume":"19","author":"Peng","year":"2013","journal-title":"World J. Gastroenterol."},{"key":"B36","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1681\/asn.v1111","article-title":"The Glomerular Slit Diaphragm Is a Modified Adherens junction","volume":"11","author":"Reiser","year":"2000","journal-title":"J. Am. Soc. Nephrol."},{"key":"B37","doi-asserted-by":"publisher","first-page":"443","DOI":"10.1016\/j.cellsig.2011.09.022","article-title":"Angiotensin II Induces Nephrin Dephosphorylation and Podocyte Injury: Role of Caveolin-1","volume":"24","author":"Ren","year":"2012","journal-title":"Cell Signal."},{"key":"B38","doi-asserted-by":"publisher","first-page":"199","DOI":"10.1083\/jcb.201410017","article-title":"The Cell Biology of Renal Filtration","volume":"209","author":"Scott","year":"2015","journal-title":"J. Cel Biol"},{"key":"B39","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1159\/000102280","article-title":"Pathogenesis of IgA Nephropathy","volume":"157","author":"Tomino","year":"2007","journal-title":"Contrib. Nephrol."},{"key":"B40","doi-asserted-by":"publisher","first-page":"3131","DOI":"10.1093\/ndt\/gfr096","article-title":"Effects and Mechanisms of Angiotensin II Receptor Blockade with Telmisartan in a Normotensive Model of Mesangioproliferative Nephritis","volume":"26","author":"Villa","year":"2011","journal-title":"Nephrol. Dial. Transpl."},{"key":"B41","doi-asserted-by":"publisher","first-page":"268","DOI":"10.3109\/0886022x.2015.1117896","article-title":"Angiotensin II Induces Reorganization of the Actin Cytoskeleton and Myosin Light-Chain Phosphorylation in Podocytes through rho\/ROCK-Signaling Pathway","volume":"38","author":"Wang","year":"2016","journal-title":"Ren. Fail."},{"key":"B42","doi-asserted-by":"publisher","first-page":"1241","DOI":"10.1038\/modpathol.2010.110","article-title":"Podocyte Number Predicts Progression of Proteinuria in IgA Nephropathy","volume":"23","author":"Xu","year":"2010","journal-title":"Mod. Pathol."},{"key":"B43","doi-asserted-by":"publisher","first-page":"1599","DOI":"10.3390\/ijms19061599","article-title":"Effects of Periostracum Cicadae on Cytokines and Apoptosis Regulatory Proteins in an IgA Nephropathy Rat Model","volume":"19","author":"Yang","year":"2018","journal-title":"Int. J. Mol. Sci."},{"key":"B44","doi-asserted-by":"publisher","first-page":"153007","DOI":"10.1016\/j.prp.2020.153007","article-title":"Tonsillar Immunology in IgA Nephropathy","volume":"216","author":"Yang","year":"2020","journal-title":"Pathol. Res. Pract."},{"key":"B45","doi-asserted-by":"publisher","first-page":"2819","DOI":"10.3969\/j.issn.1673-7202.2018.11.039","article-title":"Efficacy Study on Modified Huangqi Chifeng Decoction in Treatment of IgA Based on Real World Study","volume":"11","author":"Yu","year":"2018","journal-title":"World Chin. Med."},{"key":"B46","doi-asserted-by":"publisher","first-page":"2490","DOI":"10.3892\/etm.2018.6492","article-title":"Modified Huangqi Chifeng Decoction Inhibits Excessive Autophagy to Protect against Doxorubicin-induced N-ephrotic S-yndrome in R-ats via the PI3K\/mTOR S-ignaling P-athway","volume":"16","author":"Yu","year":"2018","journal-title":"Exp. Ther. Med."},{"key":"B47","first-page":"363","article-title":"Role of Vitamin D3 in Regulation of T Helper Cell 17 and Regulatory T-Cell Balance in Rats with Immunoglobulin a Nephropathy","volume":"8","author":"Zhang","year":"2014","journal-title":"Iran J. Kidney Dis."}],"container-title":["Frontiers in Pharmacology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2021.714584\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,7,26]],"date-time":"2021-07-26T08:14:53Z","timestamp":1627287293000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2021.714584\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,7,26]]},"references-count":47,"alternative-id":["10.3389\/fphar.2021.714584"],"URL":"https:\/\/doi.org\/10.3389\/fphar.2021.714584","relation":{},"ISSN":["1663-9812"],"issn-type":[{"value":"1663-9812","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,7,26]]},"article-number":"714584"}}