scholarly journals Downregulation of RAB7 and Caveolin-1 increases MMP-2 activity in renal tubular epithelial cells under hypoxic conditions

Open Medicine ◽  
2021 ◽  
Vol 16 (1) ◽  
pp. 1428-1437
Author(s):  
Wenmin Yu ◽  
Xiumei Ke ◽  
Meiren Li ◽  
Ping Ye ◽  
Jing Peng ◽  
...  

Abstract Tubulointerstitial fibrosis leads to tubular basement membrane thickening and accumulation of interstitial extracellular matrix (ECM). Matrix metallopeptidase-2 (MMP-2) is involved in the breakdown of ECM. Chronic hypoxia often occurs in the kidney tissues of patients with chronic kidney disease. Our previous study reported the effect of autophagy and endocytosis on MMP-2 activity in hypoxia-treated HK-2 cells. In this study, the relationship between the Ras-related protein Rab-7a (RAB7) and MMP-2 activity was further investigated. RAB7 overexpression decreased MMP-2 activity. In contrast, the results for RAB7 knockdown displayed the opposite pattern. Short hairpin RNA technology was used to knockdown Caveolin-1 (Cav-1) or Beclin-1 (Bec-1) in HK-2 cells. The two genes displayed differential effects on MMP-2 activity. Cav-1 and RAB7 interference increased MMP-2 activity. This study suggested that autophagy and endocytosis, RAB7, Cav-1, and Bec-1 may serve as potential mediators for altered MMP-2 activity.

Author(s):  
Sandhya MNVS ◽  
Vanitha K ◽  
Ramesh A

The review article focuses on the importance of adequate oxygen levels in the body as cure and therapy for many ailments. It is known that hypoxia is the cause for cellular damage and if it can be applied to major patho-physiology’s, it can be observed that slow and chronic hypoxic conditions are the cause for most of the diseases. On the contrary, providing each cell of the body with proper oxygen may be helpful in maintaining the immunity of the body and therefore treating many disease conditions. This theory, if tested may show positive results in heart related diseases, neuronal disorders, stresses, digestive disorders and the unresolved cancer too. Slow decrease in the levels of atmospheric oxygen could be a reason to induce chronic hypoxia. According to Dr. Otto Warburg, a Noble laurate, a normal cell when deprived of oxygen, may get converted to a cancerous cell, whereas a cancerous cell cannot survive in aerobic conditions. If this part of his research be concentrated on, there could be fruitful results in the treatment of cancer. To maintain adequate levels of oxygen in the body, simple yogic breathing practices are helpful. And to maintain the adequate atmospheric oxygen, trees and plants which cleanse the atmospheric air are useful. Clinical surveys on volunteers who have been practicing regular breathing exercises can prove the fact that proper and concentrated respiration could prevent many diseases. Thus, supplementing breathing exercises along with the regular treatment for cancer patients could be helpful in alleviating cancer and other diseases.


Author(s):  
Han Ouyang ◽  
Jian Wen ◽  
Kai Song ◽  
Huaying Shen

IntroductionImmunoglobulin (Ig) G deposition in patients with IgA nephro­pathy (IgAN) often indicates poor prognosis, but the relationship between IgM deposition and the clinicopathology of IgAN remains controversial. The purpose of this study is to further understand the relationship between IgM deposition and IgAN, so as to provide a basis for clinical evaluation and treatment.Material and methodsWe included a total of 839 IgAN patients from the nephropathy departments of 2 hospitals; there were 162 IgM-positive patients and 677 IgM-negative patients. Clinical and pathological data were retrospectively analysed. In addition, a multifaceted comparison was made between the IgM-positive group and the IgM-negative group.ResultsThe serum albumin and IgG levels of the IgM-positive group were lower than those of the IgM-negative group, and the levels of low-density lipo­protein, 24 h proteinuria, and IgM were higher than those of the IgM-nega­tive group. The proportion of endothelial cell proliferation (E1), segmental sclerosis or adhesion (S1), and renal tubular interstitial score in the IgM-posi­tive group were all higher than those in the IgM-negative group. Immunofluo­rescence results showed that the proportion of IgM-positive combination and IgG and C1q deposition was higher than that in the IgM-negative group.ConclusionsImmunoglobulin A nephropathy patients with IgM deposition have relatively poor clinical biochemical indicators, and the degree of renal pathological damage is also relatively serious.


1997 ◽  
Vol 272 (6) ◽  
pp. F809-F815 ◽  
Author(s):  
A. Sahai ◽  
C. Mei ◽  
A. Zavosh ◽  
R. L. Tannen

The effect of chronic hypoxia on the proliferation and dedifferentiation of LLC-PK1 cells was examined. Cultures were exposed either to hypoxia (3% O2) or normoxia (18% O2), and [3H]thymidine incorporation, cell number, and sodium-dependent glucose (Na/Glc) uptakes were assessed. Cultures exposed to hypoxia for 16 h significantly increased [3H]thymidine incorporation followed by a significant increase in cell number both at 24 and 48 h in comparison with respective normoxic controls. Cultures exposed to 24 and 72 h of hypoxia exhibited significant inhibition of Na/Glc uptake when compared with their respective normoxic counterparts. Significant inhibition of cell ATP levels were observed under hypoxic conditions. Acute reoxygenation of hypoxic cells normalized cell ATP levels without any effect on the Na/Glc uptake. Hypoxia also activated protein kinase C (PKC) at 1 and 4 h followed by a subsequent return to baseline with reactivation at 24 h, which remained sustained up to 72 h, suggesting both acute and sustained activation of PKC. Furthermore, the hypoxia-induced alterations in [3H]thymidine incorporation as well as Na/Glc uptake were mitigated by inhibitors of PKC. These results indicate that chronic hypoxia induces both proliferation and dedifferentiation of LLC-PK1 cells mediated, in part, by the activation of PKC.


2021 ◽  
Vol 10 ◽  
Author(s):  
Pei Chen ◽  
Yu-ling Zhang ◽  
Bai Xue ◽  
Guo-ying Xu

PurposeThe prognostic value of caveolin-1 in prostate cancer remains uncertain. Hence, this meta-analysis was performed to evaluate the prognostic value of caveolin-1 in prostate cancer, as well as ascertain the relationship between caveolin-1 expression and clinicopathological characteristics of prostate cancer patients.MethodsThe PubMed, Embase, Chinese National Knowledge Infrastructure and Chinese Biology Medicine databases were electronically searched to retrieve published studies on caveolin-1 expression in prostate cancer. After study selection and data extraction, the meta-analysis was conducted using Review manager 5.3 software. Odds ratio (OR) with 95% confidence interval (CI) was used to estimate the pooled effect. Funnel plot was used to assess publication bias.ResultsA total of ten studies were enrolled, which included 3976 cases of prostate cancer, 72 cases of high-grade intraepithelial neoplasia (HGPIN), and 157 normal controls. Results of the meta-analysis showed that the positive rate of caveolin-1 expression in prostate cancer was 18.28 times higher than that in normal control (OR= 18.28, 95% CI: 9.02–37.04, p<0.01), and 4.73 times higher than that in HGPIN (OR= 4.73, 95% CI: 2.38–9.42, p<0.01). The relationship between caveolin-1 and clinicopathological characteristics of prostate cancer showed that the differences in caveolin-1 expression in patients with prostate-specific antigen (PSA) >10 vs. ≤ 10 (OR=2.09, 95% CI: 1.35–3.22, p<0.01), differentiation degree low vs. medium/high (OR=2.74, 95% CI: 1.84–4.08, p<0.01), TNM stage T3+T4 vs. T1+T2 (OR=2.77, 95% CI: 1.78–4.29, p<0.01), and lymph node metastasis present vs. absent (OR=2.61, 95% CI: 1.84–3.69, p<0.01) were statistically significant. The correlation analysis between caveolin-1 and the survival time of patients with prostate cancer demonstrated that caveolin-1 was closely related to the prognosis of prostate cancer patients (HR=1.50, 95% CI: 1.28–1.76, p<0.01).ConclusionCaveolin-1 is overexpressed in prostate cancer, which can serve as a risk factor and adverse clinicopathological feature of prostate cancer. Caveolin-1 can also predict poor survival in prostate cancer patients after radical prostatectomy.


SURG Journal ◽  
1969 ◽  
Vol 2 (1) ◽  
pp. 3-10
Author(s):  
Dawn Armstrong ◽  
Lindsay Robinson

Cystic Fibrosis (CF) is characterized by a wide spectrum of phenotypic characteristics such as; deep coughing, increased mucous production, and weight loss. However, only recently was the role of inflammation on the etiology of the disease recognized. CF is characterized as a cyclic progression of infective exacerbations and stable periods initiated by the presence of Pseudomonas Aeruginosa (PA). An increase in inflammatory cytokines/mediators and a decrease in anti-inflammatory cytokines contribute to the net inflammation and overall tissue destruction of the lungs. PA is associated with the low iron status that is seen in 60-75% of the CF population, through the presence of iron sequestering siderophores which distract iron from the tissues. Iron deficiency (ID) initiates further symptoms such as; fatigue, tachycardia, weakness, brittle nails etc, in addition to those caused by CF. The colonization of PA may be the cause or a result of increased iron (ferritin) concentrations in the lungs, but independent of the original relationship, results in a decreased iron status. Iron is used by PA under hypoxic conditions such as in the fibrosis lung, as a source of energy. Studies on the relationship between CF and ID contribute a variety of possible causes although currently no direct connection has been discovered. At this stage, further studies in this area are needed. This review will primarily focus on the affects of CF on iron status in humans, and secondarily examine the effect of mediators of inflammation in respects to ID.


2021 ◽  
Vol 49 (7) ◽  
pp. 1-15
Author(s):  
Seungju Hyun ◽  
Xyle Ku

Although the relationship between grandiose and vulnerable narcissism and psychological health is widely accepted, little is known about whether and how coping strategies explain this relationship. We examined the mediating role of proactive coping in this relationship, with a sample of 280 participants from five colleges in Korea. We used four parallel multiple mediation models, and controlled for the indirect effects of coping flexibility, self-esteem, and covariates (age and gender). Results show that grandiose narcissism predicted higher life satisfaction and lower perceived stress, whereas vulnerable narcissism exhibited the opposite pattern, and all of these relationships were mediated by proactive coping. Overall, our results highlight the critical role of proactive coping in the prediction of psychological health among narcissists.


1957 ◽  
Vol 189 (3) ◽  
pp. 557-563 ◽  
Author(s):  
Walter Hollander ◽  
Robert W. Winters ◽  
T. Franklin Williams ◽  
John Bradley ◽  
Jean Oliver ◽  
...  

The effect of graded degrees of K depletion on the ability to produce a concentrated urine was studied in Sprague-Dawley rats. With increasing degrees of K depletion, as measured by the concentration of K in fat-free skeletal muscle, there was a progrossive decrease in the maximum urinary concentration. This defect of the renal concentrating mechanism appeared to be better correlated with the degree than with the duration of potassium depletion and could be demonstrated either by the use of exogenous vasopressin or by water deprivation. The potassium-deficient rats in at least one experiment developed a significant polydipsia. The data do not allow any conclusions with respect to the relationship of the polydipsia to the renal concentrating defect except that the latter at least was not severe at the onset of the increased water intake.


2020 ◽  
Vol 319 (3) ◽  
pp. L456-L470 ◽  
Author(s):  
Sheila Krishnan ◽  
Robert S. Stearman ◽  
Lily Zeng ◽  
Amanda Fisher ◽  
Elizabeth A. Mickler ◽  
...  

Mechanisms driving adaptive developmental responses to chronic high-altitude (HA) exposure are incompletely known. We developed a novel rat model mimicking the human condition of cardiopulmonary adaptation to HA starting at conception and spanning the in utero and postnatal timeframe. We assessed lung growth and cardiopulmonary structure and function and performed transcriptome analyses to identify mechanisms facilitating developmental adaptations to chronic hypoxia. To generate the model, breeding pairs of Sprague-Dawley rats were exposed to hypobaric hypoxia (equivalent to 9,000 ft elevation). Mating, pregnancy, and delivery occurred in hypoxic conditions. Six weeks postpartum, structural and functional data were collected in the offspring. RNA-Seq was performed on right ventricle (RV) and lung tissue. Age-matched breeding pairs and offspring under room air (RA) conditions served as controls. Hypoxic rats exhibited significantly lower body weights and higher hematocrit levels, alveolar volumes, pulmonary diffusion capacities, RV mass, and RV systolic pressure, as well as increased pulmonary artery remodeling. RNA-Seq analyses revealed multiple differentially expressed genes in lungs and RVs from hypoxic rats. Although there was considerable similarity between hypoxic lungs and RVs compared with RA controls, several upstream regulators unique to lung or RV were identified. We noted a pattern of immune downregulation and regulation patterns of immune and hormonal mediators similar to the genome from patients with pulmonary arterial hypertension. In summary, we developed a novel murine model of chronic hypoxia exposure that demonstrates functional and structural phenotypes similar to human adaptation. We identified transcriptomic alterations that suggest potential mechanisms for adaptation to chronic HA.


2009 ◽  
Vol 296 (2) ◽  
pp. R257-R264 ◽  
Author(s):  
Olli Arjamaa ◽  
Mikko Nikinmaa

The possibility that natriuretic peptides' effects are important in hypoxia responses of vertebrates is reviewed. Both the transcription and release of natriuretic peptides are affected by oxygen tension. Furthermore, many of the effects observed in hypoxia, such as diuresis and a reduction of plasma volume, are also caused by treatment of the animal with natriuretic peptides. Also, several clinical observations about changes in natriuretic peptide levels in, e.g., sleep apnea and cyanotic congenital heart disease, are consistent with the idea that hypoxia is involved in the etiology of conditions, in which natriuretic peptide levels increase. Virtually all published information on the relationship between oxygen and natriuretic peptides is based on human studies. Because hypoxic conditions are more common in aquatic than terrestrial environments, future studies about the possible role of natriuretic peptides in hypoxia, as well as the role of hypoxia in the evolution of natriuretic peptides, including the different subtypes, should increasingly involve also aquatic organisms.


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