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diabetic nephropathy, pathogenesis,pathology

C Randall Harrell, Bojana Simovic Markovic, Crissy Fellabaum, Aleksandar Arsenijevic, Valentin Djonov, Vladislav Volarevic
BACKGROUND: Pericytes are multipotent cells present in every vascularized tissue in the body. Despite the fact that they are well-known for more than a century, pericytes are still representing cells with intriguing properties. This is mainly because of their heterogeneity in terms of definition, tissue distribution, origin, phenotype and multi-functional properties. The body of knowledge illustrates importance of pericytes in the regulation of homeostatic and healing processes in the body...
March 9, 2018: Journal of Biomedical Science
Megan Stevens, Sebastian Oltean
Vascular endothelial growth factor A (VEGF-A) is a prominent pro-angiogenic and pro-permeability factor in the kidney. Alternative splicing of the terminal exon of VEGF-A through the use of an alternative 3' splice site gives rise to a functionally different family of isoforms, termed VEGF-Axxx b, known to have anti-angiogenic and anti-permeability properties. Dysregulation of the VEGF-Axxx /VEGF-Axxx b isoform balance has recently been reported in several kidney pathologies, including diabetic nephropathy (DN) and Denys-Drash syndrome...
February 15, 2018: Genes
Xiaodan Wang, Lihui Gao, Hua Lin, Jingling Song, Jinwen Wang, Yumin Yin, Jianghu Zhao, Xiangwei Xu, Zhenkun Li, Ling Li
Diabetic nephropathy (DN) is one of the most severe microangiopathies of diabetes mellitus and is a leading cause of end stage renal disease. Numerous studies suggest that podocyte injury contributes to progressive proteinuria. Podocytes are highly specialized, terminally differentiated cells that are unable to proliferate, autophagy plays a key role in maintaining the structure and function of podocytes. Autophagy impairment is involved in the pathogenesis of podocyte loss, which leads to massive proteinuria in DN...
February 11, 2018: European Journal of Pharmacology
Richard Van Krieken, Mandeep Marway, Pavithra Parthasarathy, Neel Mehta, Alistar J Ingram, Bo Gao, Joan C Krepinsky
Sterol regulatory element binding protein (SREBP) is an important potential mediator of kidney fibrosis, and is known to be upregulated in diabetic nephropathy. Here we evaluate the effectiveness of SREBP inhibition as treatment for diabetic nephropathy.Type 1 diabetes was induced in uninephrectomized male CD1 mice with streptozotocin. Mice were treated with the SREBP inhibitor fatostatin for 12 weeks. At endpoint, kidney function and pathology were assessed. Fatostatin inhibited the increase of both isoforms of SREBP (1 and 2) in diabetic kidneys...
February 5, 2018: Endocrinology
Federica Petrillo, Anna Iervolino, Miriam Zacchia, Adelina Simeoni, Cristina Masella, Giovanna Capolongo, Alessandra Perna, Giovambattista Capasso, Francesco Trepiccione
Background: MicroRNAs (miRNAs) are a family of short noncoding RNAs that play important roles in posttranscriptional gene regulation. miRNAs inhibit target gene expression by blocking protein translation or by inducing mRNA degradation and therefore have the potential to modulate physiological and pathological processes. Summary: In the kidney, miRNAs play a role in the organogenesis and in the pathogenesis of several diseases, including renal carcinoma, diabetic nephropathy, cystogenesis, and glomerulopathies...
December 2017: Kidney Diseases
Sergei P Boudko, Neonila Danylevych, Billy G Hudson, Vadim K Pedchenko
Collagen IV is a major constituent of basement membranes, specialized form of extracellular matrix that provides a mechanical support for tissues, serves as a polyvalent ligand for cell adhesion receptors and as a scaffold for other proteins, and plays a key role in tissue genesis, differentiation, homeostasis, and remodeling. Collagen IV underlies the pathogenesis of several human disorders including Goodpasture's disease, Alport's syndrome, diabetic nephropathy, angiopathy, and porencephaly. While the isolation of the collagen IV molecules from tissues is an ultimate prerequisite for structural and functional studies, it has been always hampered by the protein insolubility due to extensive intermolecular crosslinking and noncovalent associations with other components of basement membranes...
2018: Methods in Cell Biology
Dong Yeon Kim, Min-Kyung Kang, Sin-Hye Park, Eun-Jung Lee, Yun-Ho Kim, Hyeongjoo Oh, Yean-Jung Choi, Young-Hee Kang
Renal tubulointerstitial fibrosis is an important event in the pathogenesis of diabetic nephropathy. Under pathologic conditions, renal tubular epithelial cells undergo transition characterized by loss of cell-cell adhesion and increased cell migration. This study investigated that eucalyptol inhibited tubular epithelial cell disjunction and tubulointerstitial fibrosis stimulated by glucose. Human renal proximal tubular epithelial cells were incubated for up to 72 h in media containing 27.5 mM mannitol as osmotic controls or 33 mM glucose in the presence of 1-20 μM eucalyptol...
December 5, 2017: Oncotarget
Huan Zhang, Xiuxia Liu, Shanshan Zhou, Ye Jia, Ying Li, Yuguo Song, Junnan Wang, Hao Wu
c-Jun N-terminal kinase (JNK) contributes to the pathogenesis of diabetic nephropathy (DN). The JNK inhibitor SP600125 was reported to ameliorate DN. However, the mechanism remained unclear. We previously reported that SP600125 activated nuclear factor erythroid 2-related factor 2 (NRF2), a governor of the cellular antioxidant defense system, in the aortas of the diabetic mice. Given the critical role of NRF2 in preventing DN, the present study aimed to test whether or not NRF2 is required for SP600125's protection against DN...
December 22, 2017: Journal of Molecular Endocrinology
Zhiquan Chen, Qiuhong Chen, Junying Huang, Wenyan Gong, Yezi Zou, Lei Zhang, Peiqing Liu, Heqing Huang
Advanced glycation end products' (AGEs) modification of extracellular matrix proteins induces crosslinking, which results in thickening of the basement membrane and activating several intracellular signaling cascades, eventually promoting the pathological progression of diabetic nephropathy (DN). We have previously confirmed that casein kinase 2α (CK2α) activates the nuclear factor of kappaB (NF-κB) signaling pathway to enhance high glucose-induced expressions of fibronectin (FN) and intercellular adhesion molecule-1 (ICAM-1) in glomerular mesangial cells (GMCs)...
February 2018: Biochemical Pharmacology
Swathi Putta, Nagendra Sastry Yarla, Eswar K Kumar, Dhananjaya Bhadrapura Lakkappa, Mohammad A Kamal, Luciana Scotti, Marcus T Scotti, Ghulam Md Ashraf, George E Barreto, B Sasi Bhusana Rao, D Sarala Kumari, Gorla V Reddy, Vadim V Tarasov, Sarat Babu Imandi, Gjumrakch Aliev
Diet is an essential factor affecting the development of and risk for diabetes mellitus. In search of preventative and therapeutic strategies, it is to be considering the potential role of certain foods and their bioactive compounds to prevent the pathogenesis associated with metabolic diseases. Human consumption of anthocyanins is among the highest of all flavonoids. Epidemiological studies have suggested that the consumption of anthocyanins lowers the risk of diabetes and diabetic complications. Anthocyanins are important natural bioactive pigments responsible for red to blue colour of fruits, leaves, seeds, stems and flowers, which are present in a variety of plant species particularly in berries and cherries...
December 5, 2017: Current Medicinal Chemistry
Shifa Narula, Chanderdeep Tandon, Simran Tandon
Matrix metalloproteinases (MMPs) are members of calcium dependent-zinc containing endopeptidases that play a pivotal role in extracellular matrix (ECM) remodeling. MMPs are also known to cleave non-matrix proteins, including cell surface receptors, TNF-α, angiotensin-II, growth factors, (especially transforming growth factor-β1, ΤGF-β1) plasminogen, endothelin and other bioactive molecules. The tissue inhibitors of metalloproteinases (TIMPs) inhibit the activity of MMPs and decrease ECM degradation. Various patho-physiological conditions have been linked with the imbalance of ECM synthesis and degradation...
December 5, 2017: Current Medicinal Chemistry
Liping Bao, Jushuang Li, Dongqing Zha, Lian Zhang, Ping Gao, Tao Yao, Xiaoyan Wu
Oxidative and inflammatory damage have been suggested to play important roles in the pathogenesis of diabetic nephropathy (DN). Chlorogenic acid (CGA) is one of the most abundant polyphenols and has known immunoprotective, antioxidant and anti-inflammatory properties. In the present study, animal experiments were designed to examine the protective effects of CGA in DN, and cellular experiments were designed to explore the underlying mechanisms. CGA significantly attenuated diabetic renal damage based on histological pathology and molecular biological methods...
November 18, 2017: International Immunopharmacology
H Zaghloul, M Pallayova, O Al-Nuaimi, K R Hovis, S Taheri
The increasing global prevalence of diabetes mellitus presents a significant challenge to healthcare systems today. Although diabetic retinopathy, nephropathy and neuropathy are well-established complications of diabetes, there is a paucity of research examining the impact of dysglycaemia on the olfactory system. Olfaction is an important sense, playing a role in the safety, nutrition and quality of life of an individual, but its importance is often overlooked when compared with the other senses. As a result, olfactory dysfunction is often underdiagnosed...
January 2018: Diabetic Medicine: a Journal of the British Diabetic Association
Kengo Furuichi, Miho Shimizu, Yukio Yuzawa, Akinori Hara, Tadashi Toyama, Hiroshi Kitamura, Yoshiki Suzuki, Hiroshi Sato, Noriko Uesugi, Yoshifumi Ubara, Junichi Hohino, Satoshi Hisano, Yoshihiko Ueda, Shinichi Nishi, Hitoshi Yokoyama, Tomoya Nishino, Kentaro Kohagura, Daisuke Ogawa, Koki Mise, Yugo Shibagaki, Hirofumi Makino, Seiichi Matsuo, Takashi Wada
BACKGROUND: The Japanese classification of diabetic nephropathy reflects the risks of mortality, cardiovascular events and kidney prognosis and is clinically useful. Furthermore, pathological findings of diabetic nephropathy are useful for predicting prognoses. In this study, we evaluated the characteristics of pathological findings in relation to the Japanese classification of diabetic nephropathy and their ability to predict prognosis. METHODS: The clinical data of 600 biopsy-confirmed diabetic nephropathy patients were collected retrospectively from 13 centers across Japan...
October 27, 2017: Clinical and Experimental Nephrology
Subin Hwang, Jeeeun Park, Jinhae Kim, Hye Ryoun Jang, Ghee Young Kwon, Wooseong Huh, Yoon-Goo Kim, Dae Joong Kim, Ha Young Oh, Jung Eun Lee
AIMS: The pathogenesis of diabetic kidney disease (DKD) is complex and multifactorial; increasing evidence suggests that tubular injury and inflammatory process are involved in disease progression. We investigated the potential association of renal expression of tubular injury markers, neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), and inflammatory markers, tumor necrosis factor receptor (TNFR) 1 and 2 with renal progression in pathologically proven diabetic nephropathy (DN)...
August 24, 2017: Journal of Diabetes and its Complications
H Vernon Roohk, Asad R Zaidi, Dimple Patel
AIMS: Abnormal levels of glycated albumin (GA) are associated with the onset of both diabetes and inflammation. Although inflammation has long been associated with diabetes, this article aims to explore the underlying mechanisms of this relationship as it pertains to the role of GA. METHODS: We have reviewed 52 research articles since the year 2000. Common search terms used were "(inflammatory mediator) and GA" or "inflammation and GA". The findings have been organized according to diabetic complications with respect to the interactions of GA and inflammatory mediators...
January 2018: Inflammation Research: Official Journal of the European Histamine Research Society ... [et Al.]
Paola Pontrelli, Annarita Oranger, Mariagrazia Barozzino, Francesca Conserva, Massimo Papale, Loreto Gesualdo
Diabetic nephropathy (DN) is a chronic complication of type 2 diabetes and is the most frequent form of chronic kidney disease that can lead to end-stage renal disease. Different pathways, involved in oxidative stress, inflammation, fibrosis and cell death, are responsible for the pathogenesis of DN and regulate the progression of the disease. Ubiquitination is a fundamental pathway in intracellular signaling whose role is emerging in the regulation of molecular processes responsible for several human diseases...
October 3, 2017: Minerva Medica
P Jaswani, S Prakash, A Dhar, R K Sharma, N Prasad, S Agrawal
MicroRNAs (miRNAs) are known to suppress gene expression by binding to messenger RNAs and in turn regulate different pathophysiological processes. Transforming growth factor-β, mitogen-activated protein kinase signaling, and Wnt signaling-like major pathways associated with miRNAs are involved with kidney diseases. The discovery of miRNAs has provided new insights into kidney pathologies and may provide effective therapeutic strategies. Research has demonstrated the role of miRNAs in a variety of kidney diseases including diabetic nephropathy, lupus nephritis, hypertension, nephritic syndrome, acute kidney injury, renal cell carcinoma, and renal fibrosis...
September 2017: Indian Journal of Nephrology
Andrey A Svistunov, Vadim V Tarasov, Svetlana A Shakhmardanova, Susanna S Sologova, Ekaterina T Bagaturija, Vladimir N Chubarev, Pavel A Galenko-Yaroshevsky, George E Barreto, Gjumrakch Aliev
Urotensin II (UT II) is an important factor of cellular homeostasis. This regulatory peptide is involved in the pathophysiology of many disorders. For example, it plays an important role in the pathogenesis of acute and chronic diseases, stressful and adaptive reactions of the body, in the development of cardiovascular pathologies, metabolic syndrome, inflammation, liver cirrhosis, renal failure, diabetic nephropathy, reproductive dysfunction, progression of psychosomatic, psychoendocrinal and psychiatric disorders...
August 29, 2017: Current Protein & Peptide Science
Chao Chen, Chang Wang, Chun Hu, Yachun Han, Li Zhao, Xuejing Zhu, Li Xiao, Lin Sun
Diabetic kidney disease (DKD) is one of the primary causes of end-stage renal disease (ESRD). Early diagnosis is very important in preventing the development of DKD. Urinary albumin excretion rate (UAER) and glomerular filtration rate (GFR) are widely accepted as criteria for the diagnosis and clinical grading of DKD, and microalbuminuria has been recommended as the first clinical sign of DKD. The natural history of DKD has been divided into three stages: normoalbuminuria, microalbuminuria, and macroalbuminuria...
September 2017: Frontiers of Medicine
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