Role of heterotrimer G protein in podocyte injury / 中国临床药理学与治疗学

GPCRs are the largest membrane protein receptor superfamily in the human body, with more than 800 isoforms, and approximately 35% of Food and Drug Administration-approved and marketed drugs currently target GPCRs for the treatment of a wide range of diseases, for heart failure (beta-adrenergic receptors), peptic ulcer (histamine receptors), prostate cancer (gonadotropin receptors), hypertension (adrenergic and angiotensin receptors), pain (opioid receptors), and bronchial asthma (beta2-adrenergic receptors) examples. Although the number of GPCRs is enormous, the signaling proteins downstream of them are limited, heterotrimeric G proteins (GPs) are key proteins that signal GPCRs, translate extracellular stimuli into intracellular responses by coupling to GPCRs and initiate multiple signaling events via downstream cascades. Podocytes are an important component of the glomerular filtration barrier, and their damage is a central event in proteinuria formation and progressive glomerulosclerosis. This article reviews the regulation of GPs, their signaling and their role in podocyte injury to provide a theoretical basis for scientific research and clinical treatment of this disease.

TCM Treatment of Podocyte Injury in IgA Nephropathy Based on Multiple TCM Theories： A Review / 中国实验方剂学杂志

IgA nephropathy is the most common primary glomerular disease in China. Its clinical manifestations are mainly proteinuria， hematuria， hypertension， edema， hyperuricemia， etc. Most patients have hidden onset. 30%-40% of patients develop into end stage renal disease 10-20 years after diagnosis and rely on dialysis or kidney transplantation to maintain their lives， which is extremely harmful. Proteinuria is a common clinical manifestation of this disease， and most patients have small-to-moderate amounts of proteinuria， while 10%-24% of patients have large amounts of proteinuria. Proteinuria is the main risk factor affecting the progression of renal function in IgA nephropathy. Podocytes are the terminal part of the glomerular filtration barrier， and various factors can affect the fusion and detachment of podocyte processes that occur after podocyte injury. They are common histological lesions in IgA nephropathy and are key factors leading to proteinuria and the continuous progression of the disease. At present， Western medicine lacks targeted treatment for podocyte injury， with limited intervention methods. Drugs such as glucocorticoids are often used for treatment， and there are many adverse reactions. Based on the physiological function of podocytes， pathological and physiological changes after injury， and histological morphology of this disease， it is believed that it is closely related to traditional Chinese medicine's "Xuanfu Theory" "Kidney Collateral Syndrome" "Collateral Disease Theory"， and "Dry Blood Theory". More and more studies have shown that traditional Chinese medicine， which has the characteristics of multiple links， pathways， and targets， has a significant therapeutic effect on podocyte injury in IgA nephropathy. It can protect podocytes and reduce proteinuria and has good application and research prospects. This article systematically summarizes the mechanism and morphological changes of podocyte injury in IgA nephropathy， the understanding of podocyte injury in traditional Chinese medicine theory， and the research progress in traditional Chinese medicine treatment of podocyte injury in IgA nephropathy， so as to provide a reference for further research and application of traditional Chinese medicine intervention in podocyte injury in IgA nephropathy.

Astragaloside IV improves podocyte injury and mitochondrial dysfunction induced by high glucose and inhibits Notch pathway activation / 西安交通大学学报(医学版)

【Objective】 To investigate the protection of astragaloside IV from high glucose induced podocyte injury and mitochondrial dysfunction and its molecular mechanisms. 【Methods】 The model of podocyte injury induced by high glucose (30 mmol/L glucose) was established, and the model cells were treated with low, medium and high doses of astragaloside IV respectively; cell activity was detected by CCK-8. Apoptosis was detected by TUNEL staining. Mitochondrial membrane potential was detected by JC-1 fluorescence probe. ATP content was detected by the kit. The expression levels of apoptosis and podocyte injury related proteins and Notch pathway related proteins were detected by Western blotting. 【Results】 Compared with the control group, cell activity was decreased, apoptosis level was increased (P<0.05), anti-apoptotic protein (Bcl2) expression was decreased, and apoptosis protein (Bax, cleaved-caspase 9, cleaved-caspase 3) expressions were increased (all P<0.05) in HG group. Compared with HG group, HG+AS-IV improved cell activity and apoptosis level induced by high glucose (P<0.05), increased expression of anti-apoptotic protein (Bcl2), and decreased expressions of apoptotic protein (Bax, cleaved-caspase 9, and cleaved-caspase 3) (all P<0.05). Compared with the control group, mitochondrial dysfunction occurred in HG group, JC-1 monomer content increased, and ATP content decreased (all P<0.05). Compared with HG group, HG+AS-IV improved mitochondrial dysfunction, increased JC-1 polymer content and ATP content (P<0.05). In addition, compared with the control group, the expression of Notch pathway-related protein was decreased in HG group (P<0.05). Compared with HG group, Notch pathway-related protein expression was increased in HG+AS-IV group (all P<0.05). Molecular docking results showed that AS-IV could bind Notch1. 【Conclusion】 Astragaloside IV can improve podocyte injury and mitochondrial dysfunction induced by high glucose, possibly by inhibiting Notch pathway activation.

Role of podocyte injury signaling pathway in steroid-resistant nephrotic syndrome and research progress in traditional Chinese medicine intervention / 中国中药杂志

As one of the main diseases leading to end-stage renal disease, steroid-resistant nephrotic syndrome(SRNS) can cause serious complications such as infection. Without effective control, this disease can further lead to the malignant development of the renal function, bringing serious social and economic burdens. As previously reported, the formation of SRNS is mostly related to the podocyte injury in the body, i.e., the injury of glomerular visceral epithelial cells. Phosphatidylinositol 3-kinase(PI3K)/protein kinase B(Akt) signaling pathway, nuclear transcription factor-κB(NF-κB) signaling pathway, mammalian target of rapamycin(mTOR)/adenosine monophosphate(AMP)-activated protein kinase(AMPK), transforming growth factor(TGF)-β1/Smads, and other signaling pathways are classical signaling pathways related to podocyte injury. By regulating the expression of signaling pathways, podocyte injury can be intervened to improve the adhesion between podocyte foot processes and glomerular basement membrane and promote the function of podocytes, thereby alleviating the clinical symptoms of SRNS. Through the literature review, traditional Chinese medicine(TCM) has unique advantages and an important role in intervening in podocyte injury. In the intervention in podocyte injury, TCM, by virtue of multi-target and multi-pathway role, can regulate and intervene in podocyte injury in many ways, alleviate the clinical symptoms of SRNS, and interfere with the progress of SRNS, reflecting the unique advantages of TCM. On the other hand, TCM can directly or indirectly inhibit podocyte injury by regulating the above signaling pathways, which can not only promote the effect of hormones and immunosuppressants and shorten the course of treatment, but also reduce the toxic and side effects caused by various hormones and immunosuppressants to exert the advantages of small side effects and low price of TCM. This article reviewed TCM in the treatment of SRNS by interfering with podocyte injury-related signaling pathways and is expected to provide a reference for the in-depth study of TCM in the treatment of SRNS, as well as a theoretical basis and a new direction for the clinical application of TCM to shorten the course of treatment of SRNS and delay the progression to end-stage renal disease.

Clinical Effect of Jianpi Yangyin Guse Decoction on Podocin and Nephrin and Its Protection Against Podocyte Injury in Diabetic Nephropathy Patients with Qi and Yin Deficiency / 中国实验方剂学杂志

ObjectiveTo observe the clinical effect of Jianpi Yangyin Guse decoction on patients with diabetic nephropathy （DN），and to explore its protection against podocyte injury. MethodThe enrolled 120 DN patients at stages Ⅲ and Ⅳ and diagnosed with Qi and Yin deficiency from January 2017 to January 2020 were randomly divided into observation group and control group. During the same period，20 healthy volunteers were recruited as the normal group. In addition to the basic treatment in control group，patients in the observation group were given Jianpi Yangyin Guse decoction，and the course of treatment lasted for 3 months. The traditional Chinese medicine （TCM）syndrome score，24 h urine protein （24 h UP），urine albumin-to-creatinine ratio（UACR），liver and renal functions，D-dimer， hemoglobin A1c （HbA1c）， urine podocin and nephrin and α-smooth muscle actin （α-SMA） excretion of the two groups were observed before and after treatment，and the changes were statistically analyzed and compared with those in the normal group. ResultAfter treatment，the reduction of TCM syndrome score in the observation group was more significant than that in the control group（P<0.01）. The 24 h UP level，UACR and renal function in the observation group in the 2nd and 3rd months after treatment were lower than the conditions before treatment（P<0.05）， and those in the 3rd month after treatment were decreased compared with the conditions in the control group during the same period. The levels of podocin and nephrin in each month and the α-SMA excretion in the 3rd month after treatment in the observation group were down-regulated compared with the conditions before treatment and in the control group （P<0.05）， and the observation group had reduced α-SMA excretion in the 2nd month after treatment compared with before treatment. There were no marked changes in D-dimer and liver function of the two groups before and after treatment. The level of HbA1c in the observation group was higher than that in the control group after treatment（P<0.05）. ConclusionJianpi Yangyin Guse decoction has desirable clinical efficacy in DN patients，and its mechanism may be related to reducing podocin and nephrin and α-SMA excretion levels.

B7/CD28 costimulatory molecules involved in the immune mechanism of kidney disease / 国际儿科学杂志

The body′s specific immune response is a very complicated process involving a series of immune cells and molecules that regulate and restrict each other.At present, the pathogenesis of most kidney diseases is not clear.B7(CD80)is located on antigen-presenting cells that regulate CD4+ and CD8+ T cells and play a role in enhancing or amplifying immune responses by binding to the cellular glycoprotein CD28.It also binds to cytotoxic T lymphocyte-Antigen4(CTLA-4)to inhibit the immune response.In general, renal tissue has no or low expression of B7.However, some glomerular diseases are associated with increased B7, which reduces the ability of podocytes to attach to the glomerular basement membrane and increases inflammation and renal fibrosis.When the B7-CTLA-4 interaction occurs, the immune response is attenuated.The disease can be prevented by blocking CD28 or enhancing the CTLA-4 signal.This article reviewed the role of costimulatory molecule B7/CD28 in the pathogenesis of kidney diseases, such as pod-cell damage, primary glomerulonephritis, purpura nephritis, lupus nephritis.Furthermore, it discussed the feasibility of B7 blockers were used as targeted therapies for kidney diseases.

Intervention Mechanism of Yishen Huayu Prescription on Glomerular Podocyte Injury in Diabetic Nephropathy Rats Based on EMT Regulated by Wnt/β-catenin Pathway / 中国实验方剂学杂志

Objective:To investigate the intervention mechanism of Yishen Huayu prescription on glomerular podocyte injury in diabetic nephropathy （DN） rats based on epithelialmesenchymal transition （EMT） regulated by Wnt/<italic>β</italic>-catenin pathway. Method:The 60 SD rats were divided into control group， model group， Wnt-C59 group （0.03 g·kg^-1 Wnt/<italic>β</italic>-catenin pathway inhibitor）， low-dose group （8 g·kg^-1）， medium-dose group （16 g·kg^-1） and high-dose group （32 g·kg^-1）. After 12 weeks， various indexes ， including general signs， serum creatinine （SCr）， blood urea nitrogen （BUN）， renal index， urinary protein， blood glucose， renal pathological changes， podocyte and expressions of glomerular basement membrane injury and podocyte injury related proteins ［nephrin， synaptopodin］， Wnt/<italic>β</italic>-catenin pathway related proteins （Wnt1， <italic>β</italic>-catenin）， podocyte EMT related protein ［<italic>α</italic>-smooth muscle actin （<italic>α</italic>-SMA）， E-cadherin］， were compared between groups. Result:Compared with the control group， the renal tissue in the model group showed significant pathological changes， including diffuse thickening of glomerular mesangial matrix and severe foot process fusion， and a significant increase in SCr， BUN， renal indexes， urinary protein， blood glucose， Wnt1， <italic>β</italic>-catenin， and <italic>α</italic>-SMA expression levels （<italic>P</italic><0.05） as well as a significant decrease in nephrin， synaptopodin and E-cadherin expression levels（<italic>P</italic><0.05）. Compared with model group， SCr， BUN， renal index， urinary protein， blood glucose， Wnt1， <italic>β</italic>-catenin， and <italic>α</italic>-SMA expression levels in each intervention group significantly decreased （<italic>P</italic><0.05）， while the expression levels of nephrin， synaptopodin and E-cadherin significantly increased （<italic>P</italic><0.05）. Among intervention groups， the improvement of above indexes in high-dose Yishen Huayu prescription group was the most obvious （<italic>P</italic><0.05）， which was similar to the effect in Wnt-C59 group. Conclusion:Yishen Huayu prescription prevents podocyte EMT by inhibiting Wnt/<italic>β</italic>-catenin pathway， thereby repairing glomerular podocyte injury in rats with diabetic nephropathy.

Endoplasmic reticulum stress and proteasome pathway involvement in human podocyte injury with a truncated COL4A3 mutation / 中华医学杂志(英文版)

Background@#Collagen type IV (COL4)-related nephropathy includes a variety of kidney diseases that occur with or without extra-renal manifestations caused by COL4A3-5 mutations. Previous studies revealed several novel mutations, including three COL4A3 missense mutations (G619R, G801R, and C1616Y) and the COL4A3 chr:228172489delA c.4317delA p.Thr1440ProfsX87 frameshift mutation that resulted in a truncated NC1 domain (hereafter named COL4A3 c.4317delA); however, the mutation mechanisms that lead to podocyte injury remain unclear. This study aimed to further explore the mutation mechanisms that lead to podocyte injury.@*Methods@#Wild-type (WT) and four mutant COL4A3 segments were constructed into a lentiviral plasmid, then stably transfected into human podocytes. Real-time polymerase chain reaction and Western blotting were applied to detect endoplasmic reticulum stress (ERS)- and apoptosis-related mRNA and protein levels. Then, human podocytes were treated with MG132 (a proteasome inhibitor) and brefeldin A (a transport protein inhibitor). The human podocyte findings were verified by the establishment of a mus-Col4a3 knockout mouse monoclonal podocyte using clustered regularly interspaced short palindromic repeats/CRISPR-associated protein 9 (CRISPR/Cas9) technology.@*Results@#Our data showed that COL4A3 mRNA was significantly overexpressed in the lentivirus stably transfected podocytes. Moreover, the COL4A3 protein level was significantly increased in all groups except the COL4A3 c.4317delA group. Compared to the other test groups, the COL4A3 c.4317delA group showed excessive ERS and apoptosis. Podocytes treated with MG132 showed remarkably increased intra-cellular expression of the COL4A3 c.4317delA mutation. MG132 intervention improved higher ERS and apoptosis levels in the COL4A3 c.4317delA group. Mouse monoclonal podocytes with COL4A3 chr:82717932insA c.4852insA p.Arg1618ThrfsX4 were successfully acquired; this NC1-truncated mutation suggested a higher level of ERS and relatively remarkable level of apoptosis compared to that of the WT group.@*Conclusions@#We demonstrated that excessive ERS and ERS-induced apoptosis were involved in the podocyte injury caused by the NC1-truncated COL4A3 mutation. Furthermore, proteasome pathway intervention might become a potential treatment for collagen type IV-related nephropathy caused by a severely truncated COL4A3 mutation.

Expression of Notch pathway in diabetic nephropathy rats and intervention effect of Chinese materia medica for dispersing blood stasis and dredging collateral / 中草药

Objective To investigate the expression of Notch pathway in the kidney of diabetic nephropathy (DN) rats and the intervention effect of Chinese materia medica (CMM) for dispersing blood stasis and dredging collateral. Methods Sixty male Sprague-Dawley rats, in which ten rats were randomly selected as control group (n = 10), and the other rats were fed with high glucose and high fat diet combined with low-dose streptozotocin (STZ) ip injection as DN models. The model rats were randomly divided into model group, irbesartan group, and Huayu Tongluo Granles (HTG) group. The rats in each group were ig administered with corresponding drugs. At the end of the 16 weeks, the 24 h urinary protein was detected. The expression of Notch1, Jagged1, and Hey1 mRNA and protein in renal tissue was detected by real-time PCR, and immunohistochemical staining and western blotting assay, respectively. Results Compared with the control group, 24 h urinary protein, the mRNA and protein expression of Notch1, Jagged1, and Hey1 in model group was significantly increased (P < 0.01). Compared with the model group, 24 h urinary protein and Notch1, Jagged1, Hey1 mRNA, and protein expression of HTG group and irbesartan group was significantly decreased (P < 0.01). Conclusion CMM for dispersing blood stasis and dredging collateral can reduce 24 h urinary protein in DN rats and inhibit the high expression of Notch1, Jagged1, and Hey1 in the kidney tissue of DN rats, which may be one of the main ways to reduce proteinuria excretion.

Study on protective effect of tripterygium wilfordii polyglucosides inrats with type 2 diabetic kidney disease / 中国糖尿病杂志

Objective To observe the changes in the expression of RANK/RANKL in rat kidney treated by tripterygium wilfordii polyglucosides (TWP) in STZ induced type 2 diabetic kidney disease (DKD) and to explore its possible renoprotective mechanism.Methods T2DM animal model was established by high glucose and high fat diet plus intraperitoneal injection of STZ.The modeled rats were randomly divided into DKD group(DKD,n=8) and TWP treatment group(DT,n=8).Normal rats were taken as control group(NC,n=8).DT rats were lavaged with TWP in a dose of 50 mg/kg · d,while the NC group and DKD group were lavaged with equal volume of normal saline every day.The indicators of FPG,FIns,UAlb,BUN,Scr,and Ucr were measured before and after 12-week intervention.PAS staining was used to evaluate the pathological change of the kidney.Immunohistochemistry and Western-blot were used to observe the protein expressions of RANK,RANKL,and nephrin.Results Compared with NC group,kidney pathological changes of DN group were aggravated with higher levels of FPG,UAlb,Ccr and BUN at 12th week.The expressions of RANK[(0.27±0.05) vs (0.68±0.11)] and RANKL[(0.23± 0.07) vs (0.62±0.08)] were prominently increased in kidney in DN group than those in NC group,while the expressions of nephrin were decreased(P＜0.01).Compared with DKD group,the above indexes and renal pathological changes were improved in DT group.The expressions of RANK[(0.45 ± 0.09) vs (0.68±0.11)],and RANKL[(0.39±0.06) vs(0.62±0.08)],were markedly inhibited in DT group,while nephrin expressions were increased(P＜0.01).Conclusion TWP can protect the kidney in rats with DKD by inhibiting the expression of RANK/RANKL.

Expression of Wnt/β-catenin pathway in diabetic nephropathy rats and intervention effect of Chinese materia medica for dispersing blood stasis and dredging collaterals / 中草药

Objective: To investigate the expression of Wnt/β-catenin pathway in diabetic nephropathy (DN) rats and the intervention effect of Chinese materia medica (CMM) for dispersing blood stasis and dredging collateral. Methods: Ten rats were selected as control group from 60 rats, the remaining rats were established as DN models by feeding high glucose and high fat diet combined with low-dose streptozotocin ip injection. Model rats were randomly divided into model group, irbesartan treatment group, and CMM group. The rats in each group were ig administered with corresponding drug, at the end of the 20th week, the 24 h urinary total protein was detected. The expression levels of Wnt4 and β-catenin mRNA and protein in renal tissue were detected. Results: Compared with control group, the 24 h urinary total protein, expression of Wnt4, β-catenin mRNA, and protein significantly increased in the model group (P < 0.01). Compared with model group, 24 h urinary total protein, the expression of Wnt4, β-catenin mRNA, and protein decreased significantly in irbesartan group and CMM group (P < 0.01 or P < 0.05). Conclusion: CMM for dispersing blood stasis and dredging collateral might decrease proteinuria in DN rats. It can also inhibit the high expression of Wnt/β-catenin pathway in the kidney of diabetic nephropathy rats. The effect might be one of the main ways to reduce urinary protein excretion.

Study progress of cyclooxygenase 2/membrane associated prostaglandin E2 synthase1/prostaglandin E2 pathway in podocyte injury / 中华实用儿科临床杂志

Podocyte injury is one of the common pathological features of glomerular disease in children,and it is closely related to the development of nephropathy.Podocytopathies is the glomerular disease with abnormal structure or function in podocyte which present different pathological extent,and may progress into chronic kidney disease.Therefore,finding the effective treatment is the focus of clinical research.Recent reports have shown that cyclooxygenase 2 (COX-2) / membrane associated prostaglandin E2 synthase 1 (mPGES-1) / prostaglandin E2 (PGE2) pathway plays a critical role in podocyte injury.The inhibition of the above pathway could be a new method for the therapy of podocytopathies.This article reviews the research progress of COX-2/mPGES-1/PGE2 pathway in podocyte injury.

Study progress of cyclooxygenase 2/membrane associated prostaglandin E2 synthase1/prostaglandin E2 pathway in podocyte injury / 中华实用儿科临床杂志

Podocyte injury is one of the common pathological features of glomerular disease in children,and it is closely related to the development of nephropathy.Podocytopathies is the glomerular disease with abnormal structure or function in podocyte which present different pathological extent,and may progress into chronic kidney disease.Therefore,finding the effective treatment is the focus of clinical research.Recent reports have shown that cyclooxygenase 2 (COX-2) / membrane associated prostaglandin E2 synthase 1 (mPGES-1) / prostaglandin E2 (PGE2) pathway plays a critical role in podocyte injury.The inhibition of the above pathway could be a new method for the therapy of podocytopathies.This article reviews the research progress of COX-2/mPGES-1/PGE2 pathway in podocyte injury.

Progress of T helper cell 17,regulatory T cell,podocyte injury and primary glomerular disease / 国际儿科学杂志

In recent years,T helper cell 17(Th17),regulatory T cell(Treg) and podocyte injury attrac-ted widespread attention in the pathogenesis of primary glomerular disease. Th17 cells have the function of re-cruiting neutrophils and macrophages to the infected tissue through the secretion of cytokines such as IL-17. Treg cells have immune function, mediated immune tolerance, protecting the body against inflammatory injury. The imbalance of Th17 cells increase and Treg cells decrease could play an important role in the pathogenesis and progression of primary glomerular disease. As the important part of the glomerular filtration barrier,podocyte be-comes the focus in recent years. Study on relationship among Th17,Treg,podocyte injury and primary glomeru-lar disease will provide more theoretical basis for the prevention and treatment of primary glomerular disease.

Effect ofQiwei Granules on Renal Podocyte Injury in Diabetic Nephropathy Mice / 世界科学技术-中医药现代化

This article was aimed to study the effect ofQiwei granules on the podocyte in KK-Ay mice kidney. The 28 8-week-old male KK-Ay mice were randomly divided into the model group, low-dosage, middle-dosage and high-dosageQiwei granule group. Eight C57BL/6J mice were used as the normal control. The general conditions, blood glucose and 24 h albuminuria were recorded in the experiment. After 10-week treatment, renal indexes including serum creatinine and urea nitrogen were measured. The kidneys of mice were collected and measured. The hematoxylin and eosin (HE), Masson’s Trichrome, and periodic acid-Schiff (PAS) were used on renal tissues of mice. The immunohistochemical staining for WT-1 was made. Software analysis was combined in the calculation of renal podocyte amount. Western blot was used in the detection of nephrin protein expressions in the kidney of mice. RT-PCR was used in the detection of nephrin mRNA expression. The results showed that compared with the model group, the body weight, blood glucose, 24 h albuminuria and the serum creatinine were obviously decreased after 10-week treatment ofQiwei granules. It can effectively improve the glomerular mesangial proliferation and preserve the podocyte number. Meanwhile, after the treatment ofQiwei granules, the nephrin protein expression and mRNA expression were obviously higher than the model group. It was concluded thatQiwei granules probably managed nephrin expression to improve the podocyte injury in the diabetic nephropathy of KK-Ay mice.

Protective effect of PPAR-αagonist on PAN-induced podocyte injury / 中国药理学通报

Aim To investigate the function of fenofi-brate on PAN ( puromycin aminonucleoside )-induced podocyte injury. Methods SD female rats of 18-week-old were randomly assigned into 3 groups ( n =6 ) . Mice in PAN group and fenofibrate treated group received a single intravenous injection of PAN ( 65 mg ·kg-1 ) , while those in control group received equal volume of saline. Mice in fenofibrate treated group re-ceived 40 mg · kg-1 · d-1 of fenofibrate ( intragastric administration ) on day 1 after PAN injection , while those in PAN group and control group received equal volume of vehicle. 24 hours urine samples from all group were collected on day 0(1 day before PAN injec-tion), day 6, day 10. The 24 hours urine protein was detected by Bradford assay. All the rats were sacrificed 10 days after the induction of podocyte injury, and glo-merulus sample were collected. The expression of podocyte injury marker and transcription level in apop-tosis, podocyte cytoskeleton protein, slit diaphragm protein were evaluated by Western blot and real-time PCR. Results Compared with the control group, 10 days after injection of PAN, 24 hours urine protein was obviously increased, and the expression and transcrip-tion level of podocyte injury marker desmin, apoptosis, podocyte cytoskeleton protein, slit diaphragm protein were upregulated greatly, however, those were signifi-cantly lower in fenofibrate treated group as compared with those in PAN group. Conclusions PPAR-α ago-nist fenofibrate can ameliorate PAN-induced glomerulus podocyte injury, and the mechanism involved may be associated with inhibition of the mitochondria apopto-sis, TGF-β/Smad pathway and p38 pathway.

Podocalyxin in podocyte injury of proteinuria associated nephropathy / 国际儿科学杂志

Podocalyxin,a sialomucin most closely related to CD34,is expressed by kidney podocytes,hematopoietic progenitors,vascular endóthelia and a subset of neurons.As one of the important apical marker protein,podocalyxin plays an important role in the integrity of the structure and function of nomal podocyte,and is closely related to the prevention of proteinuria.The mechanism of podocyte injury associated with proteinuria remains unkown.The investigation of podocalyxin,a major podocyte protein,is significant in the pathogenesis and process of the primarily glomerulopathies.This paper summarizes the progresses of podocalyxin in podocyte injury of proteinuria associated nephropathy.