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TRPC6 Knockout Alleviates renal fibrosis through PI3K/AKT/GSK3B Pathway

Current Medical Science 2024年第3期44卷 589-602页

作者： An-bang SUN Fang-hua LI Lin ZHU Xi-xi ZENG Min ZHU Qing-hua LEI Yan-hong LIAO Department of Anatomy School of Basic MedicineTongji Medical CollegeHuazhong University of Science and TechnologyWuhan430030China Department of Transfusion Medicine Wuhan Hospital of Traditional Chinese and Western MedicineTongji Medical CollegeHuazhong University of Science and TechnologyWuhan430030China Department of Nephrology The First Affiliated Hospital of Zhengzhou UniversityZhengzhou450052China Department of Thoracic Surgery Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan430030China National Basic Medical Teaching Demonstration Center Tongji Medical CollegeHuazhong University of Science and TechnologyWuhan430030China Key Laboratory of Neurological Diseases of Ministry of Education Tongji Medical CollegeHuazhong University of Science and TechnologyWuhan430030China

Objective renal fibrosis is the ultimate pathway of various forms of acute and chronic kidney damage.Notably,the knockout of transient receptor potential channel 6(TRPC6)has shown promise in alleviating renal fibrosis.However,the regulatory impact of TRPC6 on renal fibrosis remains unclear.Methods In vivo,TRPC6 knockout(TRPC6−/−)mice and age-matched 129 SvEv(WT)mice underwent unilateral renal ischemia-reperfusion(uIR)injury surgery on the left renal pedicle or sham operation.Kidneys and serum were collected on days 7,14,21,and 28 after euthanasia.In vitro,primary tubular epithelial cells(PTECs)were isolated from TRPC6−/−and WT mice,followed by treatment with transforming growth factorβ1(TGFβ1)for 72 h.The anti-fibrotic effect of TRPC6−/−and the underlying mechanisms were assessed through hematoxylin-eosin staining,Masson staining,immunostaining,qRT-PCR,and Western blotting.Results Increased TRPC6 expression was observed in uIR mice and PTECs treated with TGFβ1.TRPC6−/−alleviated renal fibrosis by reducing the expression of fibrotic markers(Col-1,α-SMA,and vimentin),as well as decreasing the apoptosis and inflammation of PTECs during fibrotic progression both in vivo and in vitro.Additionally,we found that the phosphatidylinositol 3-kinase(PI3K)/protein kinase B(AKT)/glycogen synthase kinase 3 beta(GSK3β)signaling pathway,a pivotal player in renal fibrosis,was down-regulated following TRPC6 deletion.Conclusion These results suggest that the ablation of TRPC6 may mitigate renal fibrosis by inhibiting the apoptosis and inflammation of PTECs through down-regulation of the PI3K/AKT/GSK3βpathway.Targeting TRPC6 could be a novel therapeutic strategy for preventing chronic kidney disease.

关键词： transient receptor potential channel 6 ischemia-reperfusion injury renal fibrosis renal tubular epithelial cells

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Network pharmacology and experimental validation to reveal the pharmacological mechanisms of Sini decoction(四逆汤)against renal fibrosis

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Journal of Traditional Chinese Medicine 2024年第2期44卷 362-372页

作者： WANG Yan DENG Fanying LIU Shiqi WANG Yingli Department of Pharmacy Shanxi University of Chinese MedicineJinzhong 030619China Schools of Basic Medical Sciences Heilongjiang University of Chinese MedicineHaerbin 150040China

OBJECTIVE:To investigate the mechanism by which Sini decoction(四逆汤,SND)improves renal fibrosis(Rf)in rats based on transforming growth factor β1/Smad(TGF-β1/Smad)signaling pathway.METHODS:Network pharmacology was applied to obtain potentially involved signaling pathways in SND's improving effects on Rf.The targets of SND drug components and the targets of Rf were obtained by searching databases,such as the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCSMP)and GeenCard.The intersection targets of two searches were obtained and underwent signaling pathway analysis using a Venn diagram.Then experimental pharmacology was utilized to prove and investigate the effects of SND on target proteins in the TGF-β1/Smad signaling pathway.The Rf rat model was established by unilateral ureteral occlusion(UUO).The expression levels of transforming growth factor,matrix metalloproteinase-9(MMP-9),matrix metal protease-2(MMP-2),connective tissue growth factor(CTGF),and tissue inhibitor of metalloproteinase-1(TIMP-1)were determined by Masson staining of rat renal tissue,and immunohistochemical methods.The expression levels of Smad3,Smad2,and Smad7 in renal tissue were determined by Western blotting(WB).The mechanism of the improving effects of SND on Rf was investigated based on TGF-β1/Smad signaling pathway.RESULTS:A total of 12 drug components of Fuzi(Radix Aconiti Lateralis Preparata),5 drug components of Ganjiang(Rhizoma Zingiber),and 9 drug components of Gancao(Radix Glycy et Rhizoma)were obtained from the database search,and 207 shared targets were found.A total of 1063 Rf targets were found in the database search.According to the Venn diagram,in total,96 intersection targets were found in two database searches.The metabolic pathways involved included TGF-β signaling pathway,phosphatidylinositol-3-kinase/serine-threonine protein kinase signaling(PI3K/Akt)pathway,and hypoxia-inducible factor-1(HIF-1)signaling pathway.Masson staining analysis showed that compared with the model group,the renal

关键词： renal fibrosis network pharmacology transforming growth factor beta1 smad proteins Sini decoction

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Curcumin Interferes with TGF-β1-Induced fibrosis in NRK-49F Cells by Reversing ADAMTS18 Gene Methylation

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Chinese Journal of Integrative Medicine 2024年第7期30卷 600-607页

作者： XU Ben ZHANG Jia-en YE Lin YUAN Chang-wei Department of Urology Peking University First Hospital and Institute of Urology Peking UniversityNational Urological Cancer Center

Objective: To explore the molecular mechanism by which curcumin affects renal interstitial fibrosis（RIF） progression by regulating ADAM metallopeptidase with thrombospondin type 1 motif 18（ADAMTS18） methylation. Methods: NRK-49F cells RIF model were induced with transforming growth factor β1（TGF-β1）. Effects of different concentrations of curcumin（0, 10, 20, and 30 μmol/L） on cell proliferation, cell cycle, cell apoptosis as well as cyclin D1 expression were analyzed by cell counting kit-8, flow cytometry and Western blot, respectively. ADAMTS18 methylation levels were determined by methylation-specific polymerase chain reaction. ADAMTS18, fibronectin（FN）, type Ⅰ collagen（Col-Ⅰ） and alpha-smooth muscle actin（α-SMA） mRNA and protein expressions were analyzed by real-time PCR（RT-PCR） and Western blot, respectively. Meanwhile, cells were treated with 50 mmol/L 5-aza-2'-deoxycytidine（5-aza-dC, demethylation agent） for 72 h. Effect of curcumin on extracellular matrix（ECM） deposition was evaluated by immunochemical staining and Western blot. NRK-49F cells were transfected with ADAMTS18 small interfering RNA and grouped into a normal control, ADAMTS18-knock-out（KO）, and ADAMTS18-KO+ 30 μmol/L curcumin groups, and whether curcumin can reverse the effect of ADAMTS18 knockdown on RIF was evaluated. Results: Compared with the control group, TGF-β1 significantly inhibited the proliferation of NRK-49F cells, blocked the G1/G0phase, promoted cell apoptosis and inhibited cyclin D1 expression（Pfibrosis in NRK-49F cells.

关键词： renal fibrosis curcumin Chinese medicine ADAMTS18 methylation modification

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LncRNA LOC103694972 promotes fibrosis of NRK-49F cells by regulating STAT3-dependent Smad/CTGF pathway via targeting miR-29c-3p

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BIOCELL 2024年第3期48卷 501-511页

作者： YAN LI HUZHI CAI XIAOLING PENG YOUHUI LIU QINGYANG CHEN XIANGDONG LIN XINYU CHEN Department of Vascular and Tumor Intervention The First Hospital of Hunan University of Chinese MedicineChangsha410007China Department of Intensive Care Unit The First Hospital of Hunan University of Chinese MedicineChangsha410007China Department of Nursing Research The First Hospital of Hunan University of Chinese MedicineChangsha410007China Department of Intensivie Care Unit The First Hospital of Hunan University of Chinese MedicineChangsha410007China Department of Endocrinology The First Hospital of Hunan University of Chinese MedicineChangsha410007China Department of Preventive Treatment Center The First Hospital of Hunan University of Chinese MedicineChangsha410007China

Background:renalﬁbrosis is an important process in the development of chronic kidney disease.Understanding the pathogenesis andﬁnding effective treatments for renalﬁbrosis is crucial.This study aims to investigate whether a newly discovered long non-coding RNA(lncRNA)called LOC103694972 could be a potential target for treatingﬁbrosis of NRK-49F cells.Methods:LncRNA Chip was used to identify differentially expressed lncRNAs between TGF-β1-induced NRK-49F cells and normal cells.The dual-luciferase assay conﬁrmed the binding between miR-29c-3p and signal transducer and activator of transcription(STAT3),as well as between miR-29c-3p and lncRNA LOC103694972.Si-LOC103694972 and miR-29c-3p mimic were then transfected into TGF-β1-induced NRK-49F cells.Results:The study found that LOC103694972 was highly expressed in TGF-β1-induced NRK-49F cells.These cells exhibited increased cell length and activity compared to the control group.The expression levels of Collagen I,α-Smooth muscle actin(α-SMA),and tissue inhibitor of metalloproteinase(TIMP-1)were increased,while matrix Metalloproteinase 2(MMP2)and matrix Metalloproteinase 9(MMP9)expression was decreased.However,transfection with si-LOC103694972 and miR-29c-3p mimics restored cell morphology and reduced cell viability.This led to a decrease in the levels of Collagen I,α-SMA,and TIMP-1,as well as an increase in MMP2 and MMP9 expression.Additionally,TGF-β1-induced NRK-49F cells transfected with miR-29c-3p mimics activated the STAT3-Smad3/CTGF pathway.Conclusion:Based on theseﬁndings,lncRNA LOC103694972 shows promise as a target for treating renalﬁbrosis.It negatively regulates miR-29c-3p and activates the STAT3-Smad3/CTGF pathway.

关键词： renal fibrosis lncRNA LOC103694972 lncRNA Chip miR-29c-3p STAT3-Smad3/CTGF

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Efficacy and safety of activating blood circulation and removing blood stasis of Traditional Chinese Medicine for managing renal fibrosis in patients with chronic kidney disease:a systematic review and Meta-analysis

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Journal of Traditional Chinese Medicine 2023年第3期43卷 429-440页

作者： LUO Xin XIE Jing HUANG Li GAN Wenfan CHEN Ming Hospital of Chengdu University of Traditional Chinese Medicine Chengdu 610072China Chengdu University of Traditional Chinese Medicine Chengdu 610075China

OBJECTIVE:To evaluate the efficacy and safety of activating blood circulation and removing blood stasis in terms of Traditional Chinese Medicine(TCM) for managing renal fibrosis(RF) in patients with chronic kidney disease(CKD).METHODS:We searched randomized controlled trials(RCTs) from eight databases.RESULTS:Sixteen eligible studies with 1,356 participants were included in this study.Compared to treatment with Western Medicine(WM) alone,the combined treatment with activating blood circulation and removing blood stasis in terms of TCM(ARTCM) and WM to manage RF in patients with CKD significantly ameliorated type Ⅳ collagen(C-Ⅳ)(SMD:-2.17,95% CI:3.01 to-1.34),type Ⅲ procollagen(PC-Ⅲ)(SMD:-1.08,95% CI:-1.64 to-0.53),laminin(LN)(SMD:-1.28,95% CI:-1.65 to-0.90),transforming growth factor β 1(TGF-β1)(SMD:-0.65,95% CI:-1.18 to-0.12),serum creatinine(Scr)(SMD:-1.36,95% CI:-1.85 to-0.87),blood urea nitrogen(BUN)(MD:-1.51,95% CI:-2.59 to-0.43),and 24 h urine protein(24h Upro)(SMD:-1.23;95% CI:-1.96 to-0.50).The level of hyaluronic acid(HA) was similar in both types of treatment(SMD:-0.74,95% CI:-1.91 to 0.44).The subgroup analysis showed that the duration of 8 weeks might affect the concentration of C-Ⅳ,PC-Ⅲ,and LN(P < 0.05).The effectiveness of the longer duration to C-Ⅳ,PC-Ⅲ,and LN was not certain.However,the result should be interpreted in care.The safety of the treatment using ARTCM and WM could not be evaluated because a few studies had reported adverse effects.The results of the Meta-analysis were not stable enough.There was publication bias for the reports on Scr(P = 0.001),C-Ⅳ(P = 0.001),PC-Ⅲ(P = 0.026),and LN(P = 0.030) and no publication bias for the reports on BUN(P = 0.293).The quality of evidence varied from low to very low.CONCLUSIONS:The combined treatment using ARTCM and WM to manage RF in patients with CKD has some advantages over treatment with WM alone.High-quality RCTs need to be conducted for the strong support.

关键词： Medicine Chinese traditional activating blood circulation and removing blood stasis renal fibrosis efficacy safety Meta-analysis systematic review

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Chronic heat stress induces renal fibrosis and mitochondrial dysfunction in laying hens

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畜牧与生物技术杂志:英文版 2023年第5期14卷 2002-2011页

作者： Fumika Nanto‑Hara Makoto Yamazaki Hitoshi Murakami Haruhiko Ohtsu Division of Meat Animal and Poultry Research Institute of Livestock and Grassland ScienceNational Agriculture and Food Research Organization(NILGS)2 IkenodaiTsukubaIbaraki 305‑0901Japan

Background Heat stress in laying hens negatively affects egg production and shell quality by disrupting the homeo-stasis of plasma calcium and phosphorus levels.Although the kidney plays an important role in calcium and phos-phorus homeostasis,evidence regarding the effect of heat stress on renal injury in laying hens is yet to be elucidated.Therefore,the aim of this study was to evaluate the effects of chronic heat stress on renal damage in hens during laying periods.Methods A total of 16 white-leghorn laying hens(32 weeks old)were randomly assigned to two groups(n=8).One group was exposed to chronic heat stress(33°C for 4 weeks),whereas the other group was maintained at 24°C.Results Chronic heat exposure significantly increased plasma creatinine and decreased plasma albumin levels(Prenal fibrosis and the transcription levels of fibrosis-related genes(COLA1A1,αSMA,and TGF-β)in the kidney.These results suggest that renal failure and fibrosis were induced by chronic heat exposure in laying hens.In addition,chronic heat exposure decreased ATP levels and mitochondrial DNA copy number(mtDNA-CN)in renal tissue,suggesting that renal mitochondrial dysfunction occurs under conditions of heat stress.Damaged mitochondria leak mtDNAs into the cytosol and mtDNA leakage may activate the cyclic GMP-AMP synthase(cGAS)stimulator of interferon genes(STING)signaling pathway.Our results showed that chronic heat exposure activated the cGAS-STING pathway as indicated by increased expression of MDA5,STING,IRF7,MAVS,and NF-κB levels.Furthermore,the expression of pro-inflammatory cytokines(IL-12)and chemokines(CCL4 and CCL20)was upregulated in heat-stressed hens.Conclusions These results suggest that chronic heat exposure induces renal fibrosis and mitochondrial damage in laying hens.Mitochondrial damage by heat stress may activate the mtDNA-cGAS-STING signaling and cause subse-quent inflammation,which contributes to the progression of renal fibrosis and dysfunction.

关键词： cGAS-STING Heat stress Laying hens Mitochondrial DNA renal fibrosis

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An injectable micelle-hydrogel hybrid for localized and prolonged drug delivery in the management of renal fibrosis

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Acta Pharmaceutica Sinica B 2021年第3期11卷 835-847页

作者： Xianyan Qin Yingying Xu Xu Zhou Tao Gong Zhi-Rong Zhang Yao Fu Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial TechnologyWest China School of PharmacySichuan UniversityChengdu 610041China Key Laboratory of Advanced Technologies of Materials Ministry of Education and School of Materials Science and EngineeringSouthwest Jiaotong UniversityChengdu 610031China Sichuan Provincial Orthopedic Hospital Chengdu 610041China

Localized delivery,comparing to systemic drug administration,offers a unique alternative to enhance efficacy,lower dosage,and minimize systemic tissue toxicity by releasing therapeutics locally and specifically to the site of interests.Herein,a localized drug delivery platform ("plum?pudding"structure) with controlled release and long-acting features is developed through an injectable hydrogel ("pudding") crosslinked via self-assembled triblock polymeric micelles ("plum") to help reduce renal interstitial fibrosis.This strategy achieves controlled and prolonged release of model therapeutics in the kidney for up to three weeks in mice.Following a single injection,local treatments containing either anti-inflammatory small molecule celastrol or anti-TGFb antibody effectively minimize inflammation while alleviating fibrosis via inhibiting NF-k B signaling pathway or neutralizing TGF-b1 locally.Importantly,the micelle-hydrogel hybrid based localized therapy shows enhanced efficacy without local or systemic toxicity,which may represent a clinically relevant delivery platform in the management of renal interstitial fibrosis.

关键词： Hydrogel "Plum-pudding"structure Localized therapy Controlled release renal fibrosis Inflammation Celastrol Anti-TGFβantibody

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Monitoring the Progression of renal fibrosis by T2-weighted Signal Intensity and Diffusion Weighted Magnetic Resonance Imaging in Cisplatin induced Rat Models

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Chinese Medical Journal 2015年第5期128卷 626-631页

作者： Huan-Huan Wu Hui-Ru Jia Yi Zhang Le Liu Dong-Bo Xu Hao-Ran Sun Department of Radiology Tianjin Medical University Hospital Tianjin China Department of Radiology Northwest Women and Children's Hospital Tianjin Medical University Hospital Tianjin China Department of Radiology The Second Affiliated Hospital of Xi'an Jiaotong University Tianjin Medical University Hospital Tianjin China Department of Pathology Tianjin Medical University Hospital Tianjin China

Background：Diffusion weighted imaging （DWI）,with the applying of intravoxel incoherent motion model,has showed promising results in obtaining additional information about microperfusion and tubular flow associated with morphologic changes in chronic kidney diseases.The study aims to evaluate the potential of T2-weighted signal intensity （SI） and DWI with mono-and bi-exponential models to reflect the serial changes on cisplatin （CP） induced rat renal fibrosis models.Methods：Magnetic resonance exams were performed prior to and 2nd day,4th day,6th day,8th day,2nd week,3rd week and 4th week after CP injection at a 3.0T with an animal coil.Besides T2-weighted images （T2WI）,DWI of 13 b values from 0 to 1500 s/mm^2 was acquired.Apparent diffusion coefficient （ADC）,fluid fraction f,pure diffusivity D and pseudodiffusivity D＊ values were calculated.The regions of interest were placed on cortex （CO）,outer stripe of the outer medulla （OM） and inner stripe of the outer medulla （OM）,parameters were measured and compared among different time points.Five rats were scarified at each time point for pathological examination.Results：OM revealed remarkable hyperintense and broadened before it became an obscure thread,while CO demonstrated moderate hyperintense and IM didn＇t show significant change on T2WI.On all three stripes,ADC values decreased firstly then kept increasing since the 4th day;f values decreased on all stripes; D values had a tendency to increase with fluctuations but the changes didn＇t achieve statistical significance; D＊ values increased at the 2nd day then tended to be steady thereafter.Pathological findings revealed tubules epitheliums swelling followed by inflammation cells infiltration,interstitial fibrosis was observed since the 2nd week.Conclusions：All of T2-weighted SI,ADC,and biexponential models parameters vary during fibrotic process; biexponential model is superior to monoexponential model in separating changes of microperfusion together with tubular flow from pure diffusion.

关键词： Apparent Diffusion Coefficient Animal Model Histopathology Chronic Kidney Disease Kidney renal fibrosis Diffusion Weighted Imaging

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Effects of advanced glycation end products on renal fibrosis and oxidative stress in cultured NRK-49F ceils

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Chinese Medical Journal 2007年第9期120卷 787-793页

作者： YAN Hai-dong LI Xue-zhu XIE Jun-mei LI Man Department of Nephrology Eastern Hospital Tongji University Shanghai 200120 China Department of Nephrology First Affiliated Hospital of China Medical University Shengyang 110001 China Department of Nephrology Fourth People＇s Hospital of Shengyang Shengyang 110001 China

Background Advanced glycation end products （AGEs） play a critical role in the development of diabetic nephropathy. Reactive oxygen species （ROS） may play a critical role in AGEs induced growth factor expression. In this study, the effects of AGEs on transforming growth factor β1 （TGF-β1）, connective tissue growth factor （CTGF） and fibronectin （Fn） mRNA expression and oxidative stress in cultured NRK-49F cells were examined. Methods NRK-49F cells were incubated with medium containing different doses of AGEs （50, 100 or 200 μg/ml） for 24 hours, or with AGEs 100 μg/ml for different times （0, 12, 24 or 48 hours）. Cells in the serum-free medium or medium containing 25 mmol/L glucose were controls. Cells were treated with 25 mmol/L glucose and 100 μg/ml AGEs for 24 hours to determine the effects between AGEs and glucose. We clarified the role of antioxidant by pretreating cells with N-acetylcysteine （10 mmol/L）, ginkgo biloba extract （50 or 100 mg/L） for 24 hours and with 100 μg/ml AGEs for further 24 hours. Alamarblue dye assay was used to analyze cell growth; intracellular ROS generation was measured by flow cytometry; intracellular glutathione by fluorescence spectrophotometry; expressions of TGF-β1, CTGF and Fn mRNA by semiquantitative RT-PCR. Results AGEs significantly increased the expressions of TGF-β1, CTGF, Fn mRNA and intracellular ROS generation, and decreased the glutathion level in NRK-49F cells in dose- and time-dependent manners. High glucose and AGEs together significantly increased the expression of TGF-β1, CTGF and Fn mRNA, compared with AGEs and high glucose separately. Preincubation with N-acetylcysteine or ginkgo biloba extract increased GSH level, suppressed AGEs-induced oxidative stress and TGF-β1, CTGF and Fn mRNA overexpression. Conclusions AGEs can significantly increase expression of TGF-β1, CTGF, Fn mRNA in NRK-49F cells through enhancement of oxidative stress. The accumulation of AGEs may play a pivotal role in the pathogenesis of tubulointerstitial fibrosis in diabetic nephropathy. S

关键词： advanced glycation end products renal fibrosis oxidative stress ginkgo biloba extract

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MHC class Ⅱ in renal tubules plays an essential role in renal fibrosis

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Cellular & Molecular Immunology 2021年第11期18卷 2530-2540页

作者： Yunfeng Zhou Zhaokang Luo Chenghui Liao Rong Cao Zain Hussain Jie Wang Yeting Zhou Tie Chen Jie Sun Zhong Huang Baohua Liu Xiaoyan Zhang Youfei Guan Tuo Deng Department of Physiology Medical Research CenterShenzhen UniversityShenzhenChina Biological Therapy Institute Guangdong Provincial Key Laboratory of Regional Immunity and DiseasesDepartment of ImmunologyShenzhen UniversityShenzhenChina Department of Nephrology the First Affiliated Hospital of Shenzhen UniversityShenzhenChina Paul L.Foster School of Medicine Texas Tech University Health Sciences CenterEl PasoTXUSA Department of Internal Medicine Shenzhen Guangming Maternity and Child Healthcare HospitalShenzhenChina School of Pharmaceutical Sciences Shenzhen UniversityShenzhenChina Department of Biochemistry and Molecular Biology Medical Research CenterShenzhen UniversityShenzhenChina Shenzhen Key Laboratory for Systemic Aging and Intervention National Engineering Research Center for Biotechnology(Shenzhen)Medical Research CenterShenzhen UniversityShenzhenChina Department of Physiology and Pathophysiology School of Basic Medical SciencesAdvanced Institute of Medical SciencesDalian Medical UniversityDalianChina National Clinical Research Center for Metabolic Diseases Department of Metabolism and EndocrinologyThe Second Xiangya Hospital of Central South UniversityChangshaChina Key Laboratory of Diabetes Immunology Ministry of EducationChangshaChina Metabolic Syndrome Research Center Clinical Immunology CenterCentral South UniversityChangshaChina

Immunomodulation has been considered a potential therapeutic approach for chronic kidney disease(CKD).Although it has been previously reported that CD4+T cells contribute to the development of renal fibrosis after UUO,the role of MHC class Ⅱ(MHCII)in UUO-induced renal fibrosis remains largely uncharacterized.The present study reports that the expressions of MHCII molecules in renal cortical tubules are upregulated in a mouse unilateral ureter obstruction(UUO)model.Global or renal tubule-specific ablation of MHCII significantly alleviates renal fibrosis following UUO.Additionally,renal expression of profibrotic genes showcased consistent reduction in both MHCII gene deficient mouse lines.These results demonstrate that renal tubular MHCII plays an important role in pathogenesis of renal fibrosis.

关键词： Chronic kidney disease renal fibrosis MHCII Unilateral ureteral obstruction Folic acid

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