scholarly journals Drosophila Filamin exhibits a mechano-protective role during nephrocyte injury via induction of hypertrophic growth

2021 ◽  
Author(s):  
Sybille Koehler ◽  
Barry Denholm
Keyword(s):  
Protective Role ◽  
Protective Mechanism ◽  
Activity Levels ◽  
Protective Response ◽  
Hypertrophic Growth ◽  
Filtration Barrier ◽  
Kidney Glomerulus ◽  
Filamin B ◽  
Biomechanical Forces ◽  
And Function

Podocytes are highly specialized epithelial cells of the kidney glomerulus and are an essential part of the filtration barrier. Due to their position and function in the kidney, they are exposed to constant biomechanical forces such as shear stress and hydrostatic pressure. These forces increase during disease, resulting in podocyte injury and loss. The mechanism by which biomechanical forces are sensed and transduced to elicit an adaptive and protective response remains largely unknown. Here we show, using the Drosophila nephrocyte model, that the mechanosensor Cheerio (dFilamin) is central to this mechano-protective mechanism. We found expression of an activated mechanosensitive variant of Cheerio induced hypertrophy and rescued filtration function in injured nephrocytes. Additional analysis with human Filamin B confirmed this mechano-protective role. We delineated the mechano-protective pathway downstream of Cheerio and found activation of TOR and Yorkie induce nephrocyte hypertrophy, whereas their repression reversed the Cheerio-mediated hypertrophy. Although Cheerio/Filamin B pathway mediates a mechano-protective role in the face of injury, we found excessive activity resulted in a pathological phenotype, indicating activity levels must be tightly controlled. Taken together, our data suggest that Cheerio acts via the TOR and YAP pathway to induce hypertrophic growth, as a mechano-protective response to nephrocyte injury.

Lack of α8-integrin aggravates podocyte injury in experimental diabetic nephropathy

2010 ◽  
Vol 299 (5) ◽  
pp. F1151-F1157 ◽  
Author(s):  
Andrea Hartner ◽  
Nada Cordasic ◽  
Carlos Menendez-Castro ◽  
Gudrun Volkert ◽  
Julie M. Yabu ◽  
...  
Keyword(s):  
Diabetic Nephropathy ◽  
Mesangial Cells ◽  
Protective Role ◽  
Experimental Hypertension ◽  
Cell Matrix ◽  
Arterial Blood ◽  
Filtration Barrier ◽  
Glomerular Lesions ◽  
And Function ◽  
Cell Matrix Interactions

Development of diabetic nephropathy is accompanied by changes in integrin-mediated cell-matrix interactions. The α8-integrin chain is specifically expressed in mesangial cells of the glomerulus. During experimental hypertension, α8-integrin plays a protective role in the glomerulus. We hypothesized that α8-integrin is involved in maintaining the integrity of the glomerulus in diabetic nephropathy. Experimental streptozotocin (STZ) diabetes led to an increased expression and glomerular deposition of α8-integrin. To test the functional role of α8-integrin, STZ diabetes was induced in mice with a homozygous (α8−/−) or heterozygous (α8+/−) deletion of the α8-integrin gene and in wild-type litters (α8+/+). Blood glucose and mean arterial blood pressure were not different in α8−/− and α8+/+ mice after 6 wk of diabetes. However, diabetic α8−/− mice developed significantly higher albuminuria and more glomerulosclerosis than diabetic α8+/+ mice. Moreover, in diabetic α8−/− mice, the number of glomerular cells staining positive for the podocyte markers WT-1 and vimentin were reduced more prominently than in diabetic α8+/+. The filtration barrier protein nephrin was downregulated in diabetic glomeruli with the strongest reduction observed in α8−/− mice. Taken together, α8−/− mice developed more severe glomerular lesions and podocyte damage after onset of STZ diabetes than α8+/+ mice, indicating that α8-integrin is protective for the structure and function of the glomerulus and maintains podocyte integrity during the development of diabetic nephropathy.

Apigenin Alleviates Renal Fibroblast Activation through AMPK and ERK Signaling Pathways In Vitro

2020 ◽  
Vol 21 (11) ◽  
pp. 1107-1118
Author(s):  
Ningning Li ◽  
Zhan Wang ◽  
Tao Sun ◽  
Yanfei Lei ◽  
Xianghua Liu ◽  
...  
Keyword(s):  
Renal Fibrosis ◽  
Transforming Growth Factor ◽  
Therapeutic Potential ◽  
Protective Role ◽  
Fibroblast Proliferation ◽  
Fibroblast Activation ◽  
And Function ◽  
Activated Fibroblasts ◽  
Tgf Β1

Objective: Renal fibrosis is a common pathway leading to the progression of chronic kidney disease. Activated fibroblasts contribute remarkably to the development of renal fibrosis. Although apigenin has been demonstrated to play a protective role from fibrotic diseases, its pharmacological effect on renal fibroblast activation remains largely unknown. Materials and Methods: Here, we examined the functional role of apigenin in the activation of renal fibroblasts response to transforming growth factor (TGF)-β1 and its potential mechanisms. Cultured renal fibroblasts (NRK-49F) were exposed to apigenin (1, 5, 10 and 20 μM), followed by the stimulation of TGF-β1 (2 ng/mL) for 24 h. The markers of fibroblast activation were determined. In order to confirm the anti-fibrosis effect of apigenin, the expression of fibrosis-associated genes in renal fibroblasts was assessed. As a consequence, apigenin alleviated fibroblast proliferation and fibroblastmyofibroblast differentiation induced by TGF-β1. Result: Notably, apigenin significantly inhibited the fibrosis-associated genes expression in renal fibroblasts. Moreover, apigenin treatment significantly increased the phosphorylation of AMP-activated protein kinase (AMPK). Apigenin treatment also obviously reduced TGF-β1 induced phosphorylation of ERK1/2 but not Smad2/3, p38 and JNK MAPK in renal fibroblasts. Conclusion: In a summary, these results indicate that apigenin inhibits renal fibroblast proliferation, differentiation and function by AMPK activation and reduced ERK1/2 phosphorylation, suggesting it could be an attractive therapeutic potential for the treatment of renal fibrosis.

scholarly journals Cardiometabolism as an Interlocking Puzzle between the Healthy and Diseased Heart: New Frontiers in Therapeutic Applications

2021 ◽  
Vol 10 (4) ◽  
pp. 721
Author(s):  
Teresa Pasqua ◽  
Carmine Rocca ◽  
Anita Giglio ◽  
Tommaso Angelone
Keyword(s):  
Cardiac Muscle ◽  
Metabolic Networks ◽  
Mechanical Energy ◽  
Cardiac Metabolism ◽  
Protective Mechanism ◽  
Enzymatic Reactions ◽  
Carbohydrate Utilization ◽  
Pharmacological Agents ◽  
Physiological Structure ◽  
And Function

Cardiac metabolism represents a crucial and essential connecting bridge between the healthy and diseased heart. The cardiac muscle, which may be considered an omnivore organ with regard to the energy substrate utilization, under physiological conditions mainly draws energy by fatty acids oxidation. Within cardiomyocytes and their mitochondria, through well-concerted enzymatic reactions, substrates converge on the production of ATP, the basic chemical energy that cardiac muscle converts into mechanical energy, i.e., contraction. When a perturbation of homeostasis occurs, such as an ischemic event, the heart is forced to switch its fatty acid-based metabolism to the carbohydrate utilization as a protective mechanism that allows the maintenance of its key role within the whole organism. Consequently, the flexibility of the cardiac metabolic networks deeply influences the ability of the heart to respond, by adapting to pathophysiological changes. The aim of the present review is to summarize the main metabolic changes detectable in the heart under acute and chronic cardiac pathologies, analyzing possible therapeutic targets to be used. On this basis, cardiometabolism can be described as a crucial mechanism in keeping the physiological structure and function of the heart; furthermore, it can be considered a promising goal for future pharmacological agents able to appropriately modulate the rate-limiting steps of heart metabolic pathways.

Effects of erdosteine on cyclosporin-A-induced nephrotoxicity

2011 ◽  
Vol 31 (6) ◽  
pp. 565-573 ◽  
Author(s):  
M Tutanc ◽  
V Arica ◽  
N Yılmaz ◽  
A Nacar ◽  
I Zararsiz ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cyclosporin A ◽  
Protective Role ◽  
Control Group ◽  
Albino Rats ◽  
Protective Mechanism ◽  
Antioxidant Parameters ◽  
Group 2 ◽  
Wistar Albino Rats

Aim: In cyclosporin-A (CsA)-induced toxicity, oxidative stress has been implicated as a potential responsible mechanism. Therefore, we aimed to investigate the protective role of erdosteine against CsA-induced nephrotoxicity in terms of tissue oxidant/antioxidant parameters and light microscopy in rats. Materials and methods: Wistar albino rats were randomly separated into four groups. Group 1 rats treated with sodium chloride served as the control, group 2 rats were treated with CsA, group 3 with CsA plus erdosteine, and group 4 with erdosteine alone. Animals were killed and blood samples were analyzed for blood urea nitrogen (BUN), serum creatinine (Cr), uric acid (UA), total protein (TP), and albumin (ALB) levels. Kidney sections were analyzed for malondialdehyde (MDA) and nitric oxide (NO) levels and superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) activities, as well as for histopathological changes. Results: In the CsA group, MDA, GSH-Px, BUN, and Cr levels were increased. The TP and ALB levels were decreased. These changes had been improved by erdosteine administration. Other biochemical parameters did not show any significant change. Conclusion: These results indicate that erdosteine produces a protective mechanism against CsA-induced nephrotoxicity and suggest a role of oxidative stress in pathogenesis.

scholarly journals Refractive errors, ocular biometry and diabetic retinopathy: a systematic review

2020 ◽  
Author(s):  
Miao He ◽  
Haiying Chen ◽  
Wei Wang
Keyword(s):  
Systematic Review ◽  
Diabetic Retinopathy ◽  
Axial Length ◽  
Protective Factor ◽  
Posterior Vitreous Detachment ◽  
Anterior Chamber Depth ◽  
Protective Role ◽  
Protective Mechanism ◽  
Ocular Biometry ◽  
Systemic Factors

ABSTRACTDiabetic retinopathy (DR) is one of the major causes of visual impairment and blindness worldwide. The onset and progression of DR are influenced by systemic factors such as hyperglycemia and hypertension as well as ocular parameters. A better knowledge of the risk factors for DR is vital to improving the outcome of patients with DR and risk stratification. More recently, there has been increasing focus on the influence of myopia on DR development. Some observational studies have reported myopia being a protective factor for the development of DR, however the findings were inconsistent. In addition, it remains unclear whether it was myopia, axial length (AL), or other refractive factors that play the protective role. The protective mechanism against DR may be related to ocular elongation, posterior vitreous detachment, low perfusion in the retina and the abnormal cytokine profile. This systematic review will summarize the association of DR with refractory status as well as different refractive components including anterior chamber depth, refractory power of the lens, AL, and axial length-to-corneal radius ratio.

scholarly journals Thyroid hormone effect on activity levels and tissue mitochondrial biogenesis and function in young and old rats

2008 ◽  
Vol 22 (S1) ◽  
Author(s):  
Katherine A Klaus ◽  
Stephane Walrand ◽  
Dawn Morse ◽  
Jill M Schimke ◽  
Kevin R Short ◽  
...  
Keyword(s):  
Thyroid Hormone ◽  
Mitochondrial Biogenesis ◽  
Activity Levels ◽  
Hormone Effect ◽  
Old Rats ◽  
And Function

Parkinson disease: protective role and function of neuropeptides

Peptides ◽  
2021 ◽  
pp. 170713
Author(s):  
Mireille Tabikh ◽  
Charbel Chahla ◽  
Nathalie Okdeh ◽  
Herve Kovacic ◽  
Jean-Marc Sabatier ◽  
...  
Keyword(s):  
Parkinson Disease ◽  
Protective Role ◽  
And Function ◽  
Role And Function

MO263KLOTHO IS PROTECTIVE IN THE CONTEXT OF ACUTE GLOMERULAR INJURY BUT IS NOT EXPRESSED IN PODOCYTES

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Emmanuelle Charrin ◽  
Dina Dabaghie ◽  
Rik Mencke ◽  
Ilke Sen ◽  
Katja Möller-Hackbarth ◽  
...  
Keyword(s):  
Interstitial Fibrosis ◽  
Tubular Damage ◽  
Protective Effects ◽  
Glomerular Injury ◽  
Protein Levels ◽  
Filtration Barrier ◽  
Renal Histology ◽  
Distant Organ ◽  
Health And Disease ◽  
And Function

Abstract Background and Aims Podocyte integrity is crucial for the maintenance of glomerular function in health and disease. Numerous studies have reported that Klotho overexpression, or treatment with recombinant Klotho, reduces glomerular and tubular damage in mouse models of renal disease. However, the mechanism(s) of action are not fully understood. Several recent studies have also reported that Klotho is expressed in podocytes, where it protects against various types of injury. These findings conflict with previous studies, which have shown that renal Klotho expression is exclusively confined to proximal and distal tubular cells. Method To address this discrepancy and enhance our understanding of the putative glomeruloprotective effects mediated by Klotho, we examined the expression pattern of Klotho in human and mouse kidney by several different methods, and explored its protective effects by overexpressing full-length human Klotho directly in podocytes or in a distant organ (i.e. liver). Results Data at the mRNA and protein levels all converged towards an absence or very low expression of Klotho in podocytes. The generation of a podocyte-specific Klotho knockout mouse further demonstrated that its deletion did not affect glomerular structure or function. Moreover, Klotho deficiency did not worsen glomerular injury in an experimental model of glomerulonephritis (anti-GBM). However, when Klotho was overexpressed in hepatocytes (Alb-cre;hKlothofl/+ - Alb-hKL), serum Klotho increased drastically with no changes in Fgf23 or phosphate metabolism. In mice challenged with anti-GBM, renal histology and ultrastructure of the filtration barrier was less severely affected in Alb-hKL compared to WT mice. There were also significantly less albuminuria, podocyte loss and interstitial fibrosis in Alb-hKL mice compared to their WT littermates. In contrast, mice which overexpressed Klotho in podocytes (Pod-hKL) were not protected from renal injury. Conclusion Taken together, these results strongly suggest that Klotho is not expressed in any substantial amounts in human or mouse podocytes, and that membrane-bound Klotho does not play a role in podocyte biology. Importantly, our results confirm a beneficial role for soluble Klotho in protecting podocytes against injury, and in maintaining glomerular integrity and function.

scholarly journals The MscS and MscL Families of Mechanosensitive Channels Act as Microbial Emergency Release Valves

2012 ◽  
Vol 194 (18) ◽  
pp. 4802-4809 ◽  
Author(s):  
Ian R. Booth ◽  
Paul Blount
Keyword(s):  
Structure And Function ◽  
Mechanosensitive Channel ◽  
Protective Mechanism ◽  
Mechanosensitive Channels ◽  
Additional Pressure ◽  
Environmental Extremes ◽  
Life Threatening ◽  
And Function ◽  
Compare And Contrast ◽  
Plant Organelles

ABSTRACTSingle-celled organisms must survive exposure to environmental extremes. Perhaps one of the most variable and potentially life-threatening changes that can occur is that of a rapid and acute decrease in external osmolarity. This easily translates into several atmospheres of additional pressure that can build up within the cell. Without a protective mechanism against such pressures, the cell will lyse. Hence, most microbes appear to possess members of one or both families of bacterial mechanosensitive channels, MscS and MscL, which can act as biological emergency release valves that allow cytoplasmic solutes to be jettisoned rapidly from the cell. While this is undoubtedly a function of these proteins, the discovery of the presence of MscS homologues in plant organelles and MscL in fungus and mycoplasma genomes may complicate this simplistic interpretation of the physiology underlying these proteins. Here we compare and contrast these two mechanosensitive channel families, discuss their potential physiological roles, and review some of the most relevant data that underlie the current models for their structure and function.

Objectively measured physical activity and its influence on physical capacity and clinical parameters in patients with primary Sjögren’s syndrome

Lupus ◽  
2016 ◽  
Vol 26 (7) ◽  
pp. 690-697 ◽  
Author(s):  
T Dassouki ◽  
F B Benatti ◽  
A J Pinto ◽  
H Roschel ◽  
F R Lima ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Physical Activity ◽  
Physical Capacity ◽  
Activity Levels ◽  
Health Related Quality ◽  
Physical Activity Levels ◽  
Related Quality ◽  
Health Related ◽  
And Function

Objective The objectives of this paper are to objectively measure habitual physical activity levels in patients with primary Sjögren’s syndrome (pSS) with mild disease activity and to determine to which extent it may be associated with physical capacity and function and clinical features. Methods In this cross-sectional study, 29 women with pSS were objectively assessed for habitual physical activity levels (using accelerometry) and compared with 20 healthy women (CTRL) frequency-matched for physical activity levels, age, body mass index, and body fat percentage with regard to physical capacity and function, fatigue, depression, pain, and health-related quality of life. Results pSS showed 8.5 min/day of moderate-to-vigorous physical activity (MVPA) when only MVPA accumulated in bouts ≥ 10 min was considered; when considering total MVPA (including bouts < 10 min), average levels were 26.3 min/day, with 62% of pSS patients achieving the recommendation (≥ 21.4 min/day). Moreover, pSS showed lower VO2peak, lower muscle strength and function, higher fatigue, and poorer health-related quality of life when compared with CTRL ( p < 0.05). These differences (except for aerobic capacity) were sustained even when only individuals achieving the minimum of 21.4 min/day of total MVPA in both groups were compared. Finally, MVPA time was significantly correlated with aerobic conditioning, whereas total counts and sedentary time were associated with lower-body muscle strength and the bodily-pain domain of SF-36 in patients with pSS. Conclusion When compared to physical activity-matched healthy controls, pSS patients showed reduced physical capacity and function, increased fatigue and pain, and reduced health-related quality of life. Except for aerobic conditioning, these differences were sustained when only more physically active participants were compared, indicating that minimum recommended levels of physical activity for the general population may not be sufficient to counteract pSS comorbidities.

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