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https://www.readbyqxmd.com/read/28933600/a-novel-acetyltransferase-p300-inhibitor-ameliorates-hypertension-associated-cardio-renal-fibrosis
#1
Rahul Rai, Suresh K Verma, David Kim, Veronica Ramirez, Elizabeth Lux, Chengjin Li, Susmita Sahoo, Lisa D Wilsbacher, Douglas E Vaughan, Susan E Quaggin, Asish K Ghosh
Hypertension-associated end-organ damage commonly leads to cardiac and renal fibrosis. As no effective anti-fibrotic therapy currently exists, the unchecked progression of fibrogenesis manifests as cardio-renal failure and early death. We have previously shown that FATp300-p300 with intrinsic factor acetyltransferase activity-is an essential epigenetic regulator of fibrogenesis, and is elevated in several fibrotic tissues. In this report, we investigate the therapeutic efficacy of a novel FATp300 inhibitor, L002, in a murine model of hypertensive cardio-renal fibrosis...
September 21, 2017: Epigenetics: Official Journal of the DNA Methylation Society
https://www.readbyqxmd.com/read/28932127/an-in-vitro-model-of-renal-inflammation-after-ischemic-oxidative-stress-injury-nephroprotective-effects-of-a-hyaluronan-ester-with-butyric-acid-on-mesangial-cells
#2
Olga Baraldi, Francesca Bianchi, Viola Menghi, Andrea Angeletti, Anna Laura Croci Chiocchini, Maria Cappuccilli, Valeria Aiello, Giorgia Comai, Gaetano La Manna
BACKGROUND: Acute kidney injury, known as a major trigger for organ fibrosis and independent predictor of chronic kidney disease, is characterized by mesangial cell proliferation, inflammation and unbalance between biosynthesis and degradation of extracellular matrix. Therapeutic approaches targeting the inhibition of mesangial cell proliferation and matrix expansion may represent a promising opportunity for the treatment of kidney injury. An ester of hyaluronic acid and butyric acid (HB) has shown vasculogenic and regenerative properties in renal ischemic-damaged tissues, resulting in enhanced function recovery and minor degree of inflammation in vivo...
2017: Journal of Inflammation Research
https://www.readbyqxmd.com/read/28925480/the-role-of-pten-up-regulation-in-suppressing-glomerular-mesangial-cells-proliferation-and-nephritis-pathogenesis
#3
H-Y Gao, C-X Han
OBJECTIVE: Over-proliferation of mesangial cells is the major pathological change of mesangial proliferative glomerulonephritis (MPGN). PTEN-PI3K/AKT pathway plays a role in regulating proliferation of mesangial cells. Anti-thymocyte serum nephritis (ATSN) is a widely used animal model for studying MPGN. This study established ATSN model, on which the role of PTEN-PI3K/AKT signal pathway in MPGN pathogenesis was investigated. MATERIALS AND METHODS: ASTN rat model was established in parallel with control group...
August 2017: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/28921768/microrna-326-3p-ameliorates-high-glucose-and-ox-ldl-ic-induced-fibrotic-injury-in-renal-mesangial-cells-by-targeting-fc%C3%AE-riii
#4
Yiting Wang, Rui Zhang, Junlin Zhang, Fang Liu
AIM: To identify the regulatory relationship between miR-326-3p and FcγRIII, and to explore the involvement of miR-326-3p/FcγRIII/TGF-β/Smad signaling pathway in fibrotic injury, which was induced by the high glucose (HG) and oxidized low density lipoprotein immune complex (ox-LDL-IC) in mouse glomerular mesangial cells (GMCs) METHODS: Dual-luciferase reporter system and real time PCR (RT-PCR) were used to identify FcγRIII as a target gene of miR-326-3p. Lentiviral transduction was utilized to construct different expression of miR-326-3p in GMCs, which were divided into three groups: miR-326-3p mimics group (miR-326-3p group), miR-326-3p inhibitor group (miR-326-3p-inhibit group) and scramble control group (control group)...
September 17, 2017: Nephrology
https://www.readbyqxmd.com/read/28919801/transforming-growth-factor-%C3%AE-1-smad3-independent-epithelial-mesenchymal-transition-in-type-i-collagen-glomerulopathy
#5
Amanda C Brodeur, Anna M Roberts-Pilgrim, Kimberlee L Thompson, Craig L Franklin, Charlotte L Phillips
The glomerulofibrotic Col1a2-deficient mouse model demonstrates glomerular homotrimeric type I collagen deposition in mesangial and subendothelial spaces. In this report, we investigate the role of transforming growth factor β1 (TGF-β1) in myofibroblast activation and epithelial-mesenchymal transition (EMT) in this glomerulopathy. Immunohistochemical analyses of glomerular α-sma, desmin, vimentin, and proliferating cell nuclear antigen demonstrated parietal epithelial cell proliferation and EMT in late stages of the glomerulopathy in the Col1a2-deficient mice...
2017: International Journal of Nephrology and Renovascular Disease
https://www.readbyqxmd.com/read/28919632/cd36-in-chronic-kidney-disease-novel-insights-and-therapeutic-opportunities
#6
REVIEW
Xiaochun Yang, Daryl M Okamura, Xifeng Lu, Yaxi Chen, John Moorhead, Zac Varghese, Xiong Z Ruan
CD36 (also known as scavenger receptor B2) is a multifunctional receptor that mediates the binding and cellular uptake of long-chain fatty acids, oxidized lipids and phospholipids, advanced oxidation protein products, thrombospondin and advanced glycation end products, and has roles in lipid accumulation, inflammatory signalling, energy reprogramming, apoptosis and kidney fibrosis. Renal CD36 is mainly expressed in tubular epithelial cells, podocytes and mesangial cells, and is markedly upregulated in the setting of chronic kidney disease (CKD)...
September 18, 2017: Nature Reviews. Nephrology
https://www.readbyqxmd.com/read/28904360/comparison-of-prognostic-clinical-and-renal-histopathological-characteristics-of-overlapping-idiopathic-membranous-nephropathy-and-iga-nephropathy-versus-idiopathic-membranous-nephropathy
#7
Xinxin Chen, Yu Chen, Keqing Shi, Yinqiu Lv, Huan Tong, Guangju Zhao, Chaosheng Chen, Bo Chen, Duo Li, Zhongqiu Lu
Overlapping idiopathic membranous nephropathy (IMN) and immunoglobulin A nephropathy (IgAN) is rare. This study aims to investigate the unique prognostic, clinical, and renal histopathological characteristics of IMN+IgAN. This retrospective observational study included 73 consecutive cases of IMN+IgAN and 425 cases of IMN treated between September 2006 and November 2015. Prognostic and baseline clinical and histopathological data were compared between the two patient groups. Poor prognostic events included a permanent 50% reduction in eGFR, end-stage renal disease, and all-cause mortality...
September 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28889337/the-cellular-selection-between-apoptosis-and-autophagy-roles-of-vitamin-d-glucose-and-immune-response-in-diabetic-nephropathy
#8
Magda Hamzawy, Sarah Ali Abdelhameed Gouda, Laila Rashid, Mary Attia Morcos, Heba Shoukry, Nivin Sharawy
BACKGROUND AND AIMS: Apoptosis, autophagy and cell cycle arrest are cellular responses to injury which are supposed to play fundamental roles in initiation and progression of diabetic nephropathy (DN). The aims of the present study is to shed light on the potential effects of vitamin D analog 22-oxacalcitriol (OCT) on different cell responses during DN, and the possible interplay between both glucose, immune system and vitamin D in determining the cell fate. METHOD: All rats were randomly allocated into one of three groups: control, vehicle-treated DN group and OCT-treated DN group...
September 9, 2017: Endocrine
https://www.readbyqxmd.com/read/28886733/radix-puerariae-and-fructus-crataegi-mixture-inhibits-renal-injury-in-type-2-diabetes-via-decreasing-of-akt-pi3k
#9
Zhengyue Chen, Yanyan Yuan, Xinrong Zou, Mengqi Hong, Ming Zhao, Yu Zhao, Yuanping Liu, Guofu Li, Yabin Zhu, Lin Luo, Beiyan Bao, Shizhong Bu
BACKGROUND: Radix puerariae (RP) is a herbal medicines for diabetes, mainly because of anti-oxidative, insulin resistance and hypoglycemic effect. Fructus crataegi (FC) also possesses strong antioxidant activity in vitro. This study focused on the effects of herbal mixture of RP and FC (RPFC) on renal protection through a diabetic rat model. METHODS: Type 2 Diabetic model was established with high fat diet followed by injecting rats a low dose of STZ (25 mg/kg body weight)...
September 8, 2017: BMC Complementary and Alternative Medicine
https://www.readbyqxmd.com/read/28883756/sodium-butyrate-has-context-dependent-actions-on-dipeptidyl-peptidase-4-and-other-metabolic-parameters
#10
Eun-Sol Lee, Dong-Sung Lee, Prakash Raj Pandeya, Youn-Chul Kim, Dae-Gil Kang, Ho-Sub Lee, Byung-Chul Oh, Dae Ho Lee
Sodium butyrate (SB) has various metabolic actions. However, its effect on dipeptidyl peptidase 4 (DPP-4) needs to be studied further. We aimed to evaluate the metabolic actions of SB, considering its physiologically relevant concentration. We evaluated the effect of SB on regulation of DPP-4 and its other metabolic actions, both in vitro (HepG2 cells and mouse mesangial cells) and in vivo (high fat diet [HFD]-induced obese mice). Ten-week HFD-induced obese C57BL/6J mice were subjected to SB treatment by adding SB to HFD which was maintained for an additional 16 weeks...
September 2017: Korean Journal of Physiology & Pharmacology
https://www.readbyqxmd.com/read/28875388/intrinsic-renal-cells-induce-lymphocytosis-of-th22-cells-from-iga-nephropathy-patients-through-b7-ctla-4-and-ccl-ccr-pathways
#11
Lu Gan, Qiaoling Zhou, Xiaozhao Li, Chen Chen, Ting Meng, Jiaxi Pu, Mengyuan Zhu, Chenggen Xiao
IgA nephropathy (IgAN), the most common glomerulonephritis, has an unclear pathogenesis. The role of Th22 cells, which are intimately related to proteinuria and progression in IgAN, in mediating infection-related IgAN is unclear. This study aimed to characterize the association between intrinsic renal cells (tubular epithelial cells and mesangial cells) and Th22 cells in immune regulation of infection-related IgAN and to elucidate the impact of Th22 lymphocytosis; the proinflammatory cytokines IL-1, IL-6, and TNF-α; and CCL chemokines on kidney fibrosis...
September 5, 2017: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/28871938/-shendi-granules-regulates-the-balance-of-t-cell-subsets-and-down-regulates-podocalyxin-in-rats-with-mesangial-proliferative-glomerulonephritis
#12
Yiping Wang, Lei Zhang, Dong Wang, Ling Wei, Hua Jin, Xuelian Zhang, Lan Hu
Objective To observe the effect of Shendi granules on T cell subsets and podocyte marker protein in rats with mesangial proliferative glomerulonephritis (MsPGN), and study possible mechanism. Methods Totally 40 SD rats were randomly divided into the model group, valsartan group, Shendi granule group and normal group. The Shendi granule group were given 4 g/(kg.d) of Shendi granule by gavage; the valsartan group were given 10.3 mg/(kg.d) of valsartan by gavage; the model group and normal group were given the same amount of saline per day by gavage...
August 2017: Xi Bao Yu Fen Zi Mian Yi Xue za Zhi, Chinese Journal of Cellular and Molecular Immunology
https://www.readbyqxmd.com/read/28871126/mdm2-contributes-to-high-glucose-induced-glomerular-mesangial-cell-proliferation-and-extracellular-matrix-accumulation-via-notch1
#13
Chun-Tao Lei, Hui Tang, Chen Ye, Chao-Qun You, Jiao Zhang, Chun-Yun Zhang, Wei Xiong, Hua Su, Chun Zhang
Murine double minute 2 (MDM2) is an E3-ubiquitin ligase critical for various biological functions. Previous data have revealed an indispensable role of MDM2 in kidney homeostasis. However, its role in glomerular mesangial cell (GMC) proliferation and extracellular matrix (ECM) accumulation during hyperglycemia condition remains unclear. In our present study, we found that MDM2 protein level was significantly upregulated in high glucose-treated GMCs, while knocking down MDM2 by siRNA could attenuate high glucose-induced ECM accumulation and GMCs proliferation...
September 4, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28865030/drebrin-in-renal-glomeruli
#14
Wiebke K Ludwig-Peitsch
The central function of renal glomeruli is plasma ultrafiltration for primary urine production. The glomerular filtration barrier consists of a fenestrated endothelium, the glomerular basement membrane and podocytes, mesenchymal-like cells with actin filament-rich protrusions, the "foot processes." Their architecture and function are maintained and regulated by actin and several actin-binding proteins, mutations of which can be causative of glomerular diseases. Since initial immunostaining experiments had demonstrated intense drebrin reactions in renal glomeruli, the distribution of this protein was studied in detail in the kidneys of diverse mammalian species...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28861164/danggui-buxue-tang-suppresses-high-glucose-induced-proliferation-and-extracellular-matrix-accumulation-of-mesangial-cells-via-inhibiting-lncrna-pvt1
#15
Rui Zhang, Jinbo Li, Tao Huang, Xiuge Wang
BACKGROUND: Danggui Buxue Tang (DBT), a traditional Chinese medicine decoction, has been proven to have satisfactory effects on treating diabetic nephropathy (DN). In this study, we explored the potential underlying mechanism of DBT in DN treatment. METHODS: The DBT-containning serum was prepared by intragastric administration with DBT for rats. The levels of fibronectin (FN), laminin (LN) and collagen IV (COL IV) and TGF-β1 protein secreted in cell culture medium were determined by ELISA assay...
2017: American Journal of Translational Research
https://www.readbyqxmd.com/read/28858296/ccn3-suppresses-tgf-%C3%AE-1-induced-extracellular-matrix-accumulation-in-human-mesangial-cells-in-vitro
#16
Hai-Fei Liu, Hong Liu, Lin-Li Lv, Kun-Ling Ma, Yi Wen, Long Chen, Bi-Cheng Liu
Glomerular sclerosis is characterized by mesangial cell proliferation and progressive extracellular matrix (ECM) accumulation. CCN3 belongs to the CCN family of matrix proteins; increasing evidence suggests that CCN3 is an endogenous negative regulator of the ECM and fibrosis. However, the exact role of CCN3 in the accumulation of ECM remains unknown. The aim of the present study was to investigate the effects of CCN3 on TGF-β1-induced production of ECM in human mesangial cells (HMCs) in vitro. Treatment with TGF-β1 (0...
August 31, 2017: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/28854439/mpges-1-derived-pge2-contributes-to-indoxyl-sulfate-induced-mesangial-cell-proliferation
#17
Shuzhen Li, Zhenzhen Sun, Guixia Ding, Wei Gong, Jing Yu, Weiwei Xia, Songming Huang, Aihua Zhang, Yue Zhang, Zhanjun Jia
BACKGROUND/AIMS: We previously reported that indoxyl sulfate (IS) could cause mesangial cell (MC) proliferation via a cyclooxygenase (COX)-2-dependent mechanism. However, the specific prostaglandin contributing to COX-2 effect on IS-induced MC proliferation remained unknown. Thus, the present study was undertaken to examine the role of microsomal prostaglandin E synthase-1 (mPGES-1)-derived Prostaglandin E2 (PGE2) in IS-induced MC proliferation. METHODS: IS was administered to the MCs with or without mPGES-1 siRNA pretreatment to induce the MC proliferation which was determined by cell cycle analysis, DNA synthesis, and the expressions of cyclins...
August 30, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28845229/family-level-stereoselective-synthesis-and-biological-evaluation-of-pyrrolomorpholine-spiroketal-natural-product-antioxidants
#18
Alyssa L Verano, Derek S Tan
The pyranose spiroketal natural products pollenopyrroside A and shensongine A (also known as xylapyrroside A, ent-capparisine B) have been synthesized by stereoselective spirocyclizations of a common C1-functionalized glycal precursor. In conjunction with our previously reported syntheses of the corresponding furanose isomers, this provides a versatile family-level synthesis of the pyrrolomorpholine spiroketal natural products and analogues. In rat mesangial cells, hyperglycemia-induced production of reactive oxygen species, which is implicated in diabetic nephropathy, was inhibited by pollenopyrroside A and shensongine A with mid-μM IC50 values, while unnatural C2-hydroxy analogues exhibited more potent, sub-μM activity...
May 1, 2017: Chemical Science
https://www.readbyqxmd.com/read/28835419/glomerular-mesangial-cell-recruitment-and-function-requires-the-co-receptor-neuropilin-1
#19
Christina Swan Bartlett, Rizaldy Paz Scott, Isabel Anna Carota, Monika L Wnuk, Yashpal S Kanwar, Jeffrey H Miner, Susan E Quaggin
Proteinuria has been reported in cancer patients receiving agents that target the transmembrane receptor neuropilin-1 (Nrp1) suggesting potential adverse effects on glomerular function. Here we show that Nrp1 is highly expressed by mesangial cells and that genetic deletion of the Nrp1 gene from PDGFR+ mesangial cells results in proteinuric disease and glomerulosclerosis, leading to renal failure and death within 6 weeks of age in mice. The major defect is a failure of mesangial cell migration that is required to establish the mature glomerular tuft...
August 23, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/28821362/membranous-nephropathy-and-intrarenal-extramedullary-hematopoiesis-in-a-patient-with-myelofibrosis
#20
Carole Philipponnet, Pierre Ronco, Julien Aniort, Jean-Louis Kemeny, Anne-Elisabeth Heng
Kidney disease in the setting of a hematologic malignancy is common, with the frequency and type of kidney disease varying depending on the specific malignancy. Various glomerular diseases and tumor infiltration of the kidneys have been reported in patients with lymphoproliferative disorders. Descriptions of kidney involvement in myeloproliferative disorders have been much rarer. We report a case of membranous nephropathy accompanied by kidney injury in a patient with primary myelofibrosis with additional features considered related to the patient's myeloproliferative disorder...
August 16, 2017: American Journal of Kidney Diseases: the Official Journal of the National Kidney Foundation
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