FC 084LIPOTOXICITY MEDIATED BY GPR43 ACTIVATION CONTRIBUTES TO PODOCYTE INJURY IN DIABETIC NEPHROPATHY THROUGH MODULATING ERK/EGR1 PATHWAY

Abstract Background and Aims The G-protein-coupled receptor 43 (GPR43) is a post-transcriptional regulator involved in cholesterol metabolism. Our previous studies demonstrated that intracellular cholesterol accumulation contributed to podocyte injury in diabetic nephropathy (DN). This study aimed to investigate possible roles of GPR43 activation in lipid nephrotoxicity in DN and to explore its potential mechanisms. Method The experiments were conducted by using diabetic GPR43 knockout mice and cell culture model of podocytes. Renal pathological changes were checked by periodic acid schiff staining, immunohistochemical staining and transmission electron microscopy (TEM). The lipid deposition and free cholesterol contents in kidney tissues were detected by Oil Red O staining, BODIPY staining, and cholesterol quantitative assay. The protein expressions of GPR43, LC3II, p62 and related molecules of LDLR pathway in kidney tissues and podocytes were detected by real-time PCR, immunofluorescent staining, and Western blotting. Results There were decreased plasma level of LDL-cholesterol and cholesterol accumulation in kidney tissues of diabetic GPR43 knockout mice. In vitro study demonstrated that acetate, a stimulator of GPR43, increased LDLR-mediated cholesterol uptake in podocytes, accompanied with reduced cholesterol autophagic degeneration, characterized by inhibited LC3 maturation, p62 degradation, and autophagosome formation. These may evoke synergistic effects attributing to cellular cholesterol accumulation in podocytes. While genetic knockdown or pharmacological inhibition of GPR43 inhibited this effect in podocytes. Furthermore, the activation of GPR43 led to the activation of ERK1/2/EGR1 pathway in podocytes, whereas blocking ERK1/2 activity or reducing EGR1 expression reversed cholesterol influx and the inhibition of autophagy mediated by GPR43 activation in podocytes. Meanwhile, deletion of the GPR43 improved autophagy and inhibited the ERK1/2-EGR1 pathway of podocyte in diabetic mice in vivo. Conclusion Activation of the GPR43 mediated lipid nephrotoxicity contributes to podocyte injury in DN, which was mainly through the activation of ERK/EGR1 pathways. These findings suggested that the GPR43 receptor could be a potential therapeutic target for the prevention of DN progression.

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FC 005DEPOSITION OF PLATELET-DERIVED MICRO-PARTICLES IN PODOCYTES CONTRIBUTES TO DIABETIC NEPHROPATHY

Nephrology Dialysis Transplantation ◽

10.1093/ndt/gfab124.002 ◽

2021 ◽

Vol 36 (Supplement_1) ◽

Author(s):

Sijia Huang ◽

Jian Lu ◽

Pei Pei Chen ◽

Jia Xiu Zhang ◽

Xue Qi Li ◽

...

Keyword(s):

Electron Microscopy ◽

Extracellular Matrix ◽

Diabetic Nephropathy ◽

Protein Expression ◽

Inflammatory Cytokines ◽

Periodic Acid ◽

Diabetic Rats ◽

Immunofluorescent Staining ◽

Diabetic Patients ◽

Podocyte Injury

Abstract Background and Aims Diabetic nephropathy (DN) is the leading cause of end-stage renal disease in the developed world. Podocyte injury has been shown to be a critical cellular event in the progression of DN. Our previous studies demonstrated that platelet-derived microparticles (PMPs) mediated endothelial injury in diabetic rats. Therefore, this study aimed to investigate whether the PMPs deposit in podocytes and its potential effects on podocyte injury in DN. Method Deposition of PMPs in podocytes was checked by immunofluorescent staining and electron microscopy. Renal pathological change and ultra-microstructure were respectively checked by periodic acid-schiff staining and electron microscopy. The protein expression of inflammatory cytokines and extracellular matrix was measured by immunohistochemical staining and Western blot. Results The PMPs were found to be widely deposited in podocytes of glomeruli in diabetic patients and animal models and closely associated with progression of DN. Interestingly, aspirin treatment significantly inhibited accumulation of PMPs in glomeruli of diabetic rats, accompanied with alleviated mesangial matrix expansion, fusion of foot processes, decreased protein expression of inflammatory cytokines and extracellular matrix secretion. The in vitro study further confirmed the deposition of PMPs in podocytes. Moreover, PMPs stimulation induced phenotype transition of podocytes through decreased protein expression of podocin and increased protein expression of α-SMA and fibronectin, which was correlated with increased production of inflammatory cytokines. Conclusion Our findings for the first time demonstrated that deposition of PMPs in podocytes contributed to the development of DN.

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Celastrol slows the progression of early diabetic nephropathy in rats via the PI3K/AKT pathway

BMC Complementary Medicine and Therapies ◽

10.1186/s12906-020-03050-y ◽

2020 ◽

Vol 20 (1) ◽

Author(s):

Yusong Nie ◽

Chengxiao Fu ◽

Huimin Zhang ◽

Min Zhang ◽

Hui Xie ◽

...

Keyword(s):

Diabetic Nephropathy ◽

Microvascular Complications ◽

Periodic Acid ◽

Mrna Level ◽

Immunohistochemical Analysis ◽

Akt Pathway ◽

Enzyme Linked Immunosorbent Assay ◽

High Dose ◽

Periodic Acid Schiff ◽

Early Diabetic Nephropathy

Abstract Background Diabetic nephropathy serves as one of the most regular microvascular complications of diabetes mellitus and is the main factor that causes end-stage renal disease and incident mortality. As the beneficial effect and minute adverse influence of Celastrol on the renal system requires further elucidation, the renoprotective function of Celastrol in early diabetic nephropathy was investigated. Methods In high-fat and high-glucose diet/streptozotocin-induced diabetic rats which is the early diabetic nephropathy model, ALT, AST, 24 h urinary protein, blood urea nitrogen, and serum creatinine content were observed. Periodic acid-Schiff staining, enzyme-linked immunosorbent assay, immunohistochemical analysis, reverse transcription-polymerase chain reaction, and western blot analysis were used to explore the renoprotective effect of Celastrol to diabetic nephropathy rats and the underlying mechanism. Results High dose of Celastrol (1.5 mg/kg/d) not only improved the kidney function of diabetic nephropathy (DN) rats, and decreased the blood glucose and 24 h urinary albumin, but also increased the expression of LC3II and nephrin, and downregulated the expression of PI3K, p-AKT, and the mRNA level of NF-κB and mTOR. Conclusion Celastrol functions as a potential therapeutic substance, acting via the PI3K/AKT pathway to attenuate renal injury, inhibit glomerular basement membrane thickening, and achieve podocyte homeostasis in diabetic nephropathy.

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Supplementation of Abelmoschus manihot Ameliorates Diabetic Nephropathy and Hepatic Steatosis by Activating Autophagy in Mice

Nutrients ◽

10.3390/nu10111703 ◽

2018 ◽

Vol 10 (11) ◽

pp. 1703 ◽

Cited By ~ 14

Author(s):

Hwajin Kim ◽

Theodomir Dusabimana ◽

So Kim ◽

Jihyun Je ◽

Kyuho Jeong ◽

...

Keyword(s):

Diabetic Nephropathy ◽

Mitochondrial Dynamics ◽

Periodic Acid ◽

Combined Treatment ◽

Fasting Blood Glucose ◽

Diabetic Complication ◽

Protective Mechanism ◽

Protein Accumulation ◽

Leaf Extracts ◽

Periodic Acid Schiff

Diabetic nephropathy (DN) is a diabetic complication marked by albuminuria and a decline of the glomerular filtration rate. Diabetic kidneys are defective in the autophagy process and mitochondrial function and their enhancement of activity alleviates the pathology. In this paper, we developed a mouse model of DN by a combined treatment of a high-fat diet and streptozotocin after unilateral nephrectomy and supplementation with flower or leaf extracts of Abelmoschus manihot (AM) were tested. The preventive effects of the extracts on DN pathology and changes on autophagy and mitochondrial proteins were investigated. DN mice showed a significant increase in fasting blood glucose, plasma creatinine, blood urea nitrogen, and urinary albumin levels. Periodic acid–Schiff and Sirius red staining of the diabetic kidney presented a significant change in glomerular and tubular structures that was associated with podocyte loss and fibrotic protein accumulation. These changes were attenuated by AM extract treatment in DN mice. In addition, hepatic injury, proinflammatory cytokines, and lipid accumulation were decreased by AM extracts in DN mice. As a protective mechanism, AM extracts significantly increased the expression of proteins by regulating autophagy and mitochondrial dynamics, which potentially prevented the kidney and liver from accumulating pathogenic proteins and dysfunctional mitochondria, which alleviated the progression of DN.

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Yiqi Jiedu Huayu Decoction Alleviates Renal Injury in Rats With Diabetic Nephropathy by Promoting Autophagy

Frontiers in Pharmacology ◽

10.3389/fphar.2021.624404 ◽

2021 ◽

Vol 12 ◽

Author(s):

Chen Xuan ◽

Yu-Meng Xi ◽

Yu-Di Zhang ◽

Chun-He Tao ◽

Lan-Yue Zhang ◽

...

Keyword(s):

Renal Function ◽

Diabetic Nephropathy ◽

Renal Fibrosis ◽

Periodic Acid ◽

Kidney Injury ◽

Mtor Pathway ◽

Control Group ◽

Therapeutic Effects ◽

Sprague Dawley ◽

Periodic Acid Schiff

Diabetic nephropathy (DN), a common microvascular complication of diabetes, is one of the main causes of end-stage renal failure (ESRD) and imposes a heavy medical burden on the world. Yiqi Jiedu Huayu decoction (YJHD) is a traditional Chinese medicine formula, which has been widely used in the treatment of DN and has achieved stable and reliable therapeutic effects. However, the mechanism of YJHD in the treatment of DN remains unclear. This study aimed to investigate the mechanism of YJHD in the treatment of DN. Sprague-Dawley rats were randomly divided into a normal control group, a diabetic group, an irbesartan group, and three groups receiving different doses of YJHD. Animal models were constructed using streptozotocin and then treated with YJHD for 12 consecutive weeks. Blood and urine samples were collected during this period, and metabolic and renal function was assessed. Pathological kidney injury was evaluated according to the kidney appearance, hematoxylin-eosin staining, Masson staining, periodic-acid Schiff staining, periodic-acid Schiff methenamine staining, and transmission electron microscopy. The expression levels of proteins and genes were detected by immunohistochemistry, western blotting, and real-time qPCR. Our results indicate that YJHD can effectively improve renal function and alleviate renal pathological injury, including mesangial matrix hyperplasia, basement membrane thickening, and fibrosis. In addition, YJHD exhibited podocyte protection by alleviating podocyte depletion and morphological damage, which may be key in improving renal function and reducing renal fibrosis. Further study revealed that YJHD upregulated the expression of the autophagy-related proteins LC3II and Beclin-1 while downregulating p62 expression, suggesting that YJHD can promote autophagy. In addition, we evaluated the activity of the mTOR pathway, the major signaling pathway regulating the level of autophagy, and the upstream PI3K/Akt and AMPK pathways. YJHD activated the AMPK pathway while inhibiting the PI3K/Akt and mTOR pathways, which may be crucial to its promotion of autophagy. In conclusion, our study shows that YJHD further inhibits the mTOR pathway and promotes autophagy by regulating the activity of the PI3K/Akt and AMPK pathways, thereby improving podocyte injury, protecting renal function, and reducing renal fibrosis. This study provides support for the application of and further research into YJHD.

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Ameliorative Effects of Ethanolic Leaf Extract ofAzadirachta indicaon Renal Histologic Alterations in Streptozotocin-Induced Diabetic Rats

The American Journal of Chinese Medicine ◽

10.1142/s0192415x11009299 ◽

2011 ◽

Vol 39 (05) ◽

pp. 903-916 ◽

Cited By ~ 5

Author(s):

Akinola Oluwole Busayo ◽

Zatta Laura ◽

Dosumu Olufunke Olubusola ◽

Akinola Oluwafunmike Sharon ◽

Dini Luciana ◽

...

Keyword(s):

Diabetic Nephropathy ◽

Azadirachta Indica ◽

Leaf Extract ◽

Periodic Acid ◽

Diabetic Rats ◽

Periodic Acid Schiff ◽

Plasma Urea ◽

Intraperitoneal Dose ◽

Male Wistar Rats ◽

Ethanolic Leaf Extract

We studied the effect of ethanolic leaf extract of Azadirachta indica (AIE) on the microanatomy of the kidney of streptozotocin-induced diabetic rats. Thirty male Wistar rats (161–190 g) were randomly assigned to one of five treatment groups of six animals each: control, diabetic, diabetic + AIE, diabetic + metformin, AIE only. Diabetes was induced with a single intraperitoneal dose of streptozotocin (70 mg/kg body weight). AIE and metformin were administered orally for 50 days (50 d) at 500 mg/kg bw/d and 350 mg/kg bw/d, respectively. Blood glucose was estimated by glucose oxidase method; plasma urea and creatinine were assayed; and paraffin sections of the kidney were stained by periodic acid-Schiff technique. Untreated diabetic rats exhibited marked hyperglycemia. Renal histopathology of these animals showed features of diabetic nephropathy, with nodular glomerulosclerosis and vacuolation of proximal tubule cells (Armanni-Ebstein phenomenon). These feature were absent in the diabetic rats treated with AIE. Besides, plasma urea and creatinine were not significantly different from the control in this group (p > 0.05), in contrast to the untreated diabetic rats, where significant increases in these markers (p < 0.05). These findings showed that the leaf extract of Azadirachta indica ameliorates hyperglycemia and diabetic nephropathy in rats.

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Dianthus superbus Improves Glomerular Fibrosis and Renal Dysfunction in Diabetic Nephropathy Model

Nutrients ◽

10.3390/nu11030553 ◽

2019 ◽

Vol 11 (3) ◽

pp. 553 ◽

Cited By ~ 5

Author(s):

Jung Yoon ◽

Ji Park ◽

Hye Kim ◽

Hong-Guang Jin ◽

Hye Kim ◽

...

Keyword(s):

Diabetic Nephropathy ◽

Renal Dysfunction ◽

Transforming Growth Factor ◽

Mesangial Cells ◽

Periodic Acid ◽

Transforming Growth Factor Β ◽

Collagen Type Iv ◽

Model Assessment ◽

Periodic Acid Schiff ◽

Monocyte Chemoattractant Protein 1

Glomerular fibrosis is caused by an accumulation of intercellular spaces containing mesangial matrix proteins through either diffused or nodular changes. Dianthus superbus has been used in traditional medicine as a diuretic, a contraceptive, and an anti-inflammatory agent. The aim of this study was to investigate the effects of Dianthus superbus-EtOAc soluble fraction (DS-EA) on glomerular fibrosis and renal dysfunction, which has been implicated in diabetic nephropathy in human renal mesangial cells and db/db mice. DS-EA was administered to db/db mice at 10 or 50 mg/kg/day for 8 weeks. DS-EA treatment significantly ameliorated blood glucose, insulin, the homeostasis model assessment of insulin resistance (HOMA-IR) index, and HbA1c in diabetic mice. DS-EA decreased albumin excretion, creatinine clearance (Ccr), and plasma creatinine levels. DS-EA also ameliorated the levels of kidney injury molecules-1 (KIM-1) and C-reactive protein. DS-EA reduced the periodic acid-Schiff (PAS) staining intensity and basement membrane thickening in glomeruli of the diabetic nephropathy model. In addition, DS-EA suppressed transforming growth factor-β (TGF-β)/Smad signaling. Collagen type IV, a glomerular fibrosis biomarker, was significantly decreased upon DS-EA administration. DS-EA pretreatment attenuated levels of inflammation factors such as intracellular cell adhesion molecule-1 (ICAM-1) and monocyte chemoattractant protein-1 (MCP-1). DS-EA inhibited the translocation of nuclear factor kappa B (NF-κB) in Angiotensin II (Ang II)-stimulated mesangial cells. These findings suggest that DS-EA has a protective effect against renal inflammation and fibrosis. Therefore, DS-EA may serve as a potential therapeutic agent targeting glomerulonephritis and glomerulosclerosis, which lead to diabetic nephropathy.

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Triphala Ameliorates Nephropathy via Inhibition of TGF-β1 and Oxidative Stress in Diabetic Rats

Pharmacology ◽

10.1159/000508238 ◽

2020 ◽

Vol 105 (11-12) ◽

pp. 681-691

Author(s):

Sachin V. Suryavanshi ◽

Mayuresh S. Garud ◽

Kalyani Barve ◽

Veeranjaneyulu Addepalli ◽

Sachin V. Utpat ◽

...

Keyword(s):

Oxidative Stress ◽

Diabetic Nephropathy ◽

Periodic Acid ◽

Diabetic Rats ◽

Antidiabetic Activity ◽

Periodic Acid Schiff ◽

Safe Alternative ◽

Traditional Medicines ◽

Alternative Treatment Option ◽

Tgf Β1

Introduction: Advanced glycation end products, oxidative stress, and TGF-β expression play a crucial role in pathophysiology of diabetic nephropathy. Inhibition of oxidative stress and TGF-β expression by natural traditional medicines may give an economic and safe alternative treatment option. Triphala churna, a traditional medicine, has been proved to have potent antioxidant activity, and individual components of it have shown significant antidiabetic activity. Hence, the present study was designed to study the effect of Triphala churna in diabetic nephropathy in rats. Methods: Diabetes was induced in rats by administration of streptozotocin (55 mg/kg i.p.). Four weeks after induction of diabetes, the animals were treated with Triphala churna at the doses of 250, 500, and 1,000 mg/kg for next 4 weeks. Various biochemical and urine parameters such as glucose, creatinine, blood urea nitrogen (BUN), total protein, and albumin were assessed at the end of study. Creatinine clearance, BUN clearance, and glomerular filtration rate were determined. Oxidative stress parameters such as malondialdehyde, catalase, reduced glutathione, and superoxide dismutase were determined in kidney tissues. TGF-β1 expression was measured with ELISA, immunohistochemistry, and western blot techniques. Histopathology study was carried out with haemotoxylin and eosin, periodic acid-Schiff, and Masson’s trichrome staining to determine histological changes. Results: Treatment with Triphala churna significantly improved urine parameters. Triphala churna treatment also improved plasma proteins, albumin, creatinine, and BUN levels. The oxidative stress was reduced in the kidney with the treatment of Triphala churna. Histopathological studies revealed that Triphala churna reduced kidney damage. Immunohistochemistry, ELISA, and western blotting study revealed that treatment with Triphala decreased the expression of TGF-β in kidney tissues. Conclusion: From the results, it can be concluded that Triphala churna has a significant nephroprotective effect because of its capability of inhibiting oxidative stress and TGF-β in diabetes.

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Diagnosis of non-neoplastic renal diseases in renal mass biopsies

Journal of Onco-Nephrology ◽

10.1177/2399369319833699 ◽

2019 ◽

Vol 3 (1) ◽

pp. 49-52 ◽

Cited By ~ 1

Author(s):

Melissa Y Tjota ◽

Alexander J Gallan ◽

Gladell P Paner ◽

Tatjana Antic ◽

Arieh L Shalhav ◽

...

Keyword(s):

Diabetic Nephropathy ◽

Renal Mass ◽

Tissue Sample ◽

Periodic Acid ◽

Renal Parenchyma ◽

Renal Diseases ◽

Small Renal Masses ◽

Periodic Acid Schiff ◽

Renal Masses ◽

Pathologic Evaluation

Purpose: As up to 25% of renal neoplasms may be benign, renal function preservation is often a priority in the management of small renal masses. Studies have demonstrated the occurrence of non-neoplastic renal diseases in nephrectomy specimens, but this has not been studied in the setting of renal mass biopsy. Therefore, we conducted this study to determine the feasibility of evaluating the non-neoplastic renal parenchyma in such a limited tissue sample. Methods: We identified 117 needle biopsies for renal lesions in adults from the Department of Pathology archives (2007–2017). Additional stains for periodic acid–Schiff or Jones methenamine silver were obtained as needed. Results: Of 117 cases, non-neoplastic renal parenchyma was absent in 91 cases (78%) and present in 26 cases (22%). Review of the hematoxylin and eosin slides identified 6 cases (5%) with significant diffuse and/or nodular mesangial sclerosis. Additional review of the periodic acid–Schiff and Jones’ stains demonstrated two cases that showed diffuse and focally nodular mesangial sclerosis that was consistent with diabetic nephropathy. Conclusions: The needle biopsy is increasingly useful in guiding the management of patients with small renal masses. Although less than 25% of renal mass biopsies had sufficient non-neoplastic renal parenchyma for pathologic evaluation, medical renal diseases, such as diabetic nephropathy, could be diagnosed. On the contrary, the biopsy specimens for urothelial lesions rarely yield sufficient adjacent non-neoplastic renal parenchyma for pathologic evaluation.

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Tubular overexpression of Gremlin in transgenic mice aggravates renal damage in diabetic nephropathy

AJP Renal Physiology ◽

10.1152/ajprenal.00023.2015 ◽

2015 ◽

Vol 309 (6) ◽

pp. F559-F568 ◽

Cited By ~ 24

Author(s):

Vanessa Marchant ◽

Alejandra Droguett ◽

Graciela Valderrama ◽

M. Eugenia Burgos ◽

Daniel Carpio ◽

...

Keyword(s):

Diabetic Nephropathy ◽

Renal Damage ◽

Transforming Growth Factor ◽

Mesangial Cells ◽

Interstitial Fibrosis ◽

Smooth Muscle Actin ◽

Periodic Acid ◽

Kidney Tissue ◽

Renal Tubules ◽

Periodic Acid Schiff

Diabetic nephropathy (DN) is currently a leading cause of end-stage renal failure worldwide. Gremlin was identified as a gene differentially expressed in mesangial cells exposed to high glucose and in experimental diabetic kidneys. We have described that Gremlin is highly expressed in biopsies from patients with diabetic nephropathy, predominantly in areas of tubulointerstitial fibrosis. In streptozotocin (STZ)-induced experimental diabetes, Gremlin deletion using Grem1 heterozygous knockout mice or by gene silencing, ameliorates renal damage. To study the in vivo role of Gremlin in renal damage, we developed a diabetic model induced by STZ in transgenic (TG) mice expressing human Gremlin in proximal tubular epithelial cells. The albuminuria/creatinuria ratio, determined at week 20 after treatment, was significantly increased in diabetic mice but with no significant differences between transgenic (TG/STZ) and wild-type mice (WT/STZ). To assess the level of renal damage, kidney tissue was analyzed by light microscopy (periodic acid-Schiff and Masson staining), electron microscopy, and quantitative PCR. TG/STZ mice had significantly greater thickening of the glomerular basement membrane, increased mesangial matrix, and podocytopenia vs. WT/STZ. At the tubulointerstitial level, TG/STZ showed increased cell infiltration and mild interstitial fibrosis. In addition, we observed a decreased expression of podocin and overexpression of monocyte chemoattractant protein-1 and fibrotic-related markers, including transforming growth factor-β1, Col1a1, and α-smooth muscle actin. Together, these results show that TG mice overexpressing Gremlin in renal tubules develop greater glomerular and tubulointerstitial injury in response to diabetic-mediated damage and support the involvement of Gremlin in diabetic nephropathy.

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Baicalin improves podocyte injury in rats with diabetic nephropathy by inhibiting PI3K/Akt/mTOR signaling pathway

Open Medicine ◽

10.1515/med-2021-0335 ◽

2021 ◽

Vol 16 (1) ◽

pp. 1286-1298

Author(s):

Yi Ou ◽

Wenjuan Zhang ◽

Shaopeng Chen ◽

Haihua Deng

Keyword(s):

Diabetic Nephropathy ◽

Signaling Pathway ◽

Periodic Acid ◽

Fasting Blood Glucose ◽

Kidney Tissue ◽

Mtor Signaling ◽

Dependent Manner ◽

Mtor Signaling Pathway ◽

Podocyte Injury ◽

Treatment Groups

Abstract Objective To investigate the effect of baicalin on diabetic nephropathy (DN) rats and podocytes and its mechanism. Methods The rat models with DN were established by high-fat and high-sugar diet and intraperitoneal injection of streptozotocin. The fasting blood glucose (FBG) and weight of rats in each group were measured at 0, 1, 2, 3, and 4 weeks. Their biochemical indicators, expression of inflammatory, and antioxidant factors were measured using an automatic biochemical analyzer together with ELISA. Hematoxylin–eosin staining and periodic acid-schiff staining were used to observe the morphological changes in the kidneys of rats in each group. Finally, the expressions of related molecules and PI3K/Akt/mTOR signaling pathway proteins in renal tissues and podocytes were examined by qRT-PCR and Western blot. Results Compared with the DN group, the FBG and weight, serum creatinine, blood urea nitrogen, total cholesterol, triacylglycerol, microalbumin, and albumin/creatinine ratio were all significantly decreased in the Baicalin treatment groups in a concentration-dependent manner. The levels of inflammatory factors in kidney tissue and podocytes were decreased. In addition, the activities of lactate dehydrogenase and malondialdehyde in tissue were decreased, while the superoxide dismutase was increased. The pathological sections showed that glomerular atrophy and glomerular basement membrane thickening caused by hyperglycemia were improved in the Baicalin treatment groups. Meanwhile, baicalin inhibited the downregulation of Nephrin and Podocin expressions and upregulation of Desmin expression caused by DN, and inhibited the expressions of p-PI3K, p-Akt, and p-mTOR proteins. Conclusion Baicalin slows down podocyte injury caused by DN by inhibiting the activity of PI3K/Akt/mTOR signaling pathway.

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