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Background:
Abnormal expression of serum TGF-β1 was found in patients with diabetic nephropathy. However, the association of TGF-β1 with the risk of diabetic nephropathy remains unknown. The present study was undertaken to investigate whether such an association exists.
Methods:
We searched the Chinese VIP, Wangfang, China National Knowledge Inf...
Context in source publication
Context 1
... shown in the flow diagram in Fig 1, a total of 74777 articles were obtained from the initial database search. After perusing the title and abstracts, 132 randomized controlled trials deemed relevant for TGF-β1 level analysis in diabetic nephropathy patients remained for additional reviewing. ...
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Citations
... Using microarray analysis, Liu et al. [33] showed that TGF-β1 was one of the differentially expressed genes in early diabetic nephropathy (DN) and non-diabetic samples as its expression was upregulated. Further, serum TGF-β1 has been identified as a risk factor for developing DN and may even serve as a potential biomarker, as shown in a meta-analysis conducted by Mou et al. [34]. However, clinical trials have not demonstrated the effectiveness of anti-TGF-β1 antibodies in preventing DKD progression, suggesting a complex role of TGF-β1 in DKD [35]. ...
Diabetic kidney disease (DKD) is a major cause of end-stage renal disease and imposes a heavy global economic burden; however, little is known about its complicated pathophysiology. Investigating the cellular crosstalk involved in DKD is a promising avenue for gaining a better understanding of its pathogenesis. Nonetheless, the cellular crosstalk of podocytes and endothelial cells in DKD is better understood than that of mesangial cells (MCs) and renal tubular epithelial cells (TECs). As the significance of MCs and TECs in DKD pathophysiology has recently become more apparent, we reviewed the existing literature on the cellular crosstalk of MCs and TECs in the context of DKD to acquire a comprehensive understanding of their cellular communication. Insights into the complicated mechanisms underlying the pathophysiology of DKD would improve its early detection, care, and prognosis.
... So far, different biomarkers including B2M, A1M, KIM-1, NGAL, TNFR-1, TNFR-2, and TGF-β have been suggested as predictors of DN progression by meta-analysis studies [52][53][54][55][56][57]; However, as far as we know, there is no meta-analysis assessing the potential of NT-proBNP and TnT in predicting the DN progression in diabetic patients. The obtained data from the present meta-analysis can shed a light on the potential of two cardiac biomarkers, NT-proBNP and TnT, in providing a comprehensive predicting model for DN progression. ...
Aims:
A meta-analysis was done to investigate the association of two cardiac biomarkers of N-terminal prohormone of B-type natriuretic peptide (NT-proBNP) and circulating troponin T (TnT) with the progression of diabetic nephropathy (DN).
Methods:
A thorough search of the PubMed, Scopus, and Web of Science databases was done until June 2022. The outcome (progression of DN) was described as either of the followings: a) eGFR decline, b) albuminuria, c) end-stage renal disease, or d) mortality. A pooled analysis of eligible studies was performed using random-effect models to compensate for the differences in measurement standards between the studies. We further carried out subgroup analyses to examine our results' robustness and find the source of heterogeneity. A sensitivity analysis was performed to assess the influence of individual studies on the pooled result and the funnel plot and Egger's test were used to assess publication bias.
Results:
For NT-proBNP, 8741 participants from 14 prospective cohorts, and for TnT, 7292 participants from 9 prospective cohorts were included in the meta-analysis. Higher NT-proBNP levels in diabetic patients were associated with a higher probability of DN progression (relative risk [RR]: 1.67, 95% confidence interval [CI]: 1.44 to 1.92). Likewise, elevated levels of TnT were associated with an increased likelihood of DN (RR: 1.57, 95% CI: 1.34 to 1.83). The predictive power of both biomarkers for DN remained significant when the subgroup analyses were performed. The risk estimates were sensitive to none of the studies. The funnel plot and Egger's tests indicated publication bias for both biomarkers. Hence, trim and fill analysis was performed to compensate for this putative bias and the results remained significant both for NT-proBNP (RR: 1.50, 95% CI: 1.31 to 1.79) and TnT (RR: 1.35, 95% CI 1.15 to 1.60).
Conclusions:
The increased blood levels of TnT and NT-proBNP can be considered as predictors of DN progression in diabetic individuals. PROSPERO registration code: CRD42022350491.
... Pathologically, TGF β1 serves a vital role in the promotion of glomerulosclerosis, tubular fibrosis, and decrease infiltration rate of the glomerulus, TGF β1 also increase the albumin level, water level, electrolytes levels, and the level of glucose excreted via the urine of diabetic patients (44). The elevated number of TGF-β1 receptors expressed is reported to be necessary for fibrosis and remodelling of tissues in many organs during the progression of the disease, which includes glomerular fibrosis in the kidney (47). Several findings have shown that TGF-β1 assists in the progress of albuminuria in diabetics (44). ...
Introduction: Diabetic nephropathy is among the major causes of mortality and morbidity in type 1 & type 2 diabetes and is strongly associated with cardiovascular disease outcomes. Higher blood pressure and poor glycaemic control were reported to be the most common risk factors influencing the progress of diabetic nephropathy. This study was designed to determine the diagnostic and prognostic potential of the serum transformation growth factor β1 [TGF β1] in normoalbuminuric, microalbuminuric, macroalbuminuric and end-stage renal disease type 2 diabetic nephropathy patients. Materials and Methods: The transformation growth factor β1 was measured using ELISA test kits and serum creatinine was assessed by the modified Jaffe method while estimated glomerular filtration rate [EGFR] in the study was evaluated by the MDRD equation (adjusted for four variables). Results: The levels of serum transformation growth factor β1 and urine albumin/creatinine ratio were significantly increased (p < 0.05) across the diabetes nephropathy stages, while the estimated glomerular filtration rate was progressively decreased (p < 0.05). Serum creatinine was significantly increased (p < 0.05) with the progression of diabetic nephropathy. Conclusion: Transformation growth factor β1 might have the potentials to be used as a diagnostic and prognostic marker for diabetic nephropathy.
... TGFA 38 and TGFB 39 have shown a pathologic contribution in diabetic kidney disease. TGFB is also reported associated with type 2 diabetic nephropathy 40 . ALKP has been investigated as an independent predictor for diabetes incidence 41,42 . ...
Longitudinal deep multiomics profiling, which combines biomolecular, physiological, environmental and clinical measures data, shows great promise for precision health. However, integrating and understanding the complexity of such data remains a big challenge. Here we utilize an individual-focused bottom-up approach aimed at first assessing single individuals’ multiomics time series, and using the individual-level responses to assess multi-individual grouping based directly on similarity of their longitudinal deep multiomics profiles. We used this individual-focused approach to analyze profiles from a study profiling longitudinal responses in type 2 diabetes mellitus. After generating periodograms for individual subject omics signals, we constructed within-person omics networks and analyzed personal-level immune changes. The results identified both individual-level responses to immune perturbation, and the clusters of individuals that have similar behaviors in immune response and which were associated to measures of their diabetic status.
... A meta-analysis revealed that elevated serum levels of TGF-β are present in diabetic patients, which poses a high risk for nephropathy [98]. Therefore, a study on mice evaluated the use of pyrrole-imidazole (PI) polyamide, promoter inhibitors targeting TGF-β1, which resulted in improvement of podocyte injury [99]. ...
Chronic kidney disease (CKD) is one of the major health problems of the modern age. It represents an important public health challenge with an everlasting rising prevalence, which reached almost 700 million by the year 2017. Therefore, it is very important to identify patients at risk for CKD development and discover risk factors that cause the progression of the disease. Several studies have tackled this conundrum in recent years, novel markers have been identified, and new insights into the pathogenesis of CKD have been gained. This review summarizes the evidence on markers of inflammation and their role in the development and progression of CKD. It will focus primarily on cytokines, chemokines, and cell adhesion molecules. Nevertheless, further large, mul-ticenter studies are needed to establish the role of these markers and confirm possible treatment options in everyday clinical practice.
... However, a recent meta-analysis found that TGF-β1 levels were significantly increased in patients with diabetic nephropathy compared to those with diabetes alone and healthy controls. 19 This is supported by studies that have found that a renin-angiotensin system blockade leads to a reduction in urinary TGF-β1 levels in diabetic nephropathy, 20 an effect shown to be enhanced by vitamin D replacement. 21 Overall, the evidence for the use of TGF-β as a biomarker is not available yet, but a potential problem arises from its lack of specificity to diabetic nephropathy. ...
In an ideal world, every condition would have a sensitive and specific marker that could be measured in a noninvasive or minimally invasive way. Instead, the medical community depends on invasive biomarkers, which carry inherent risks, to make a diagnosis and plan treatment. In this review article, the current state of research into biomarkers for a range of kidney diseases is discussed, beginning with those biomarkers that are already in clinical use and then moving to conditions for which no validated biomarker yet exists. This review focusses on diabetic nephropathy at the proteinuric end of the spectrum and antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis at the nephritic end. An interesting feature is that the same biomarker, monocyte chemoattractant protein-1 (MCP-1, also known as CCL2), has been identified as a potential target in both conditions, which suggests a shared pathogenic process that results in two very distinct clinical presentations. One of the major limiting features of research into this area, particularly for ANCA-associated vasculitis, is the recruitment of a sufficient number of patients to generate strong enough evidence to justify the biomarker’s routine use; this overlap in biomarkers may enable research in one condition to be applied more generally. In addition to their role as biomarkers, these molecules are also therapeutic targets, and some early research has been carried out to investigate this. Overall, this review brings together research from diverse fields to focus attention on the outstanding areas and the future areas that warrant further investigation.
... They reported that the levels of serum and urinary TGF-β1 were significantly increased in T2DM and T2DN. Mou et al. [76] assessed 9 reports that included 264 patients and 227 healthy controls in a meta-analysis to study the relationship between serum TGF-β1 levels and the risk of diabetic nephropathy. Their study indicated that increased serum TGF-β1 levels in DM patients were associated with a high risk of renal involvement. ...
Background
Diabetes mellitus (DM) is divided into four different etiological categories: type 1 DM (T1DM), type 2 DM (T2DM), other specific types, and gestational DM. One severe complication of T2DM is type 2 diabetic nephropathy (T2DN). The possible association of serum transforming growth factor-β1 (TGF-β1) levels and the TGF-β1 T869C gene polymorphism with patient susceptibility to T2DN in Chinese population is unclear at present. This study was conducted to assess these relationships in Chinese population by a meta-analysis.
Methods
Association reports were searched and pulled from the Cochrane Library, the China Biological Medicine Database (CBM), and PubMed on March 1, 2018, and eligible studies were selected and used for calculations. The results were expressed as weighted mean differences (MD) for continuous data. Odds ratios (OR) were used to express the results for dichotomous data. Additionally, 95% confidence intervals (CI) were calculated.
Results
Forty-eight reports for the relationship between serum TGF-β1 levels and the risk of T2DN and 13 studies on the association of the TGF-β1 T869C gene polymorphism with susceptibility to T2DN in Chinese population were retrieved from this study. Serum TGF-β1 levels in the T2DM group were higher than those in the normal control group (MD = 17.30, 95% CI: 12.69–21.92, P < 0.00001). The serum TGF-β1 level in the T2DN group was significantly higher than that in the normal control group (MD = 70.03, 95% CI: 60.81–79.26, P < 0.00001;). The serum TGF-β1 level in the T2DN group was significantly higher than that in the T2DM group (MD = 56.18, 95% CI: 46.96–65.39, P < 0.00001). Serum TGF-β1 levels in T2DM patients with microalbuminuria were increased when compared with those in T2DM patients with normoalbuminuria. Furthermore, serum TGF-β1 levels in T2DM patients with macroalbuminuria were increased when compared with those in T2DM patients with microalbuminuria. The TGF-β1 T allele, TT allele and CC genotype were associated with T2DN susceptibility in Chinese population (T: OR = 0.74, 95% CI: 0.59–0.92, P = 0.007; TT: OR = 0.55, 95% CI: 0.31–0.96, P = 0.04; CC: OR = 1.38, 95% CI: 1.14–1.67, P = 0.001).
Conclusions
High levels of TGF-β1 are associated with susceptibility to T2DM, T2DN and the progression of proteinuria in T2DN patients in Chinese population. Further, the TGF-β1 T allele, and TT genotype were protective factors against the onset of T2DN and CC genotype was a risk factor for the susceptibility of T2DN in Chinese populations.
... Increased expression level of TGF-b1 has been treated as an indicator for the development of certain human diseases. In a recent study, Mou et al. reported that serum levels of TGF-b1 levels were significantly higher in patients with diabetic nephropathy than those in healthy controls, and the increased TGF-b1 level in serum can be used to effectively distinguish diabetic nephropathy patients from people with normal physiological conditions [14]. In another study, increased serum TGF-b1 levels were proved to be responsible for the decreased chemotherapy response of non-small cell lung cancer cells, which is a major cause of unsatisfactory treatment outcomes and poor prognosis of those patients [15]. ...
Background
Transforming growth factor (TGF)-β1 is involved in the pathogenesis of coronary artery disease (CAD), but the mechanism of its action remains unclear. Our study aimed to investigate the role of TGF-β1 in CAD and to explore the possible mechanisms.
Material/Methods
A total of 60 CAD patients and 54 healthy people were included in this study. Blood samples were drawn from each participant to prepare serum. ELISA was utilized to measure serum level of TGF-β1. TGF-β1 expression vector, TGF-β1 siRNA, and TIMP-1 siRNA were transfected into human primary coronary artery endothelial cell (HCAEC) line cells, and expression of TGF-β1 sphingosine kinase 1 (SPHK1) and TIMP metallopeptidase inhibitor 1 (TIMP-1) was detected by Western blot. Cell apoptosis was detected by MTT assay.
Results
Serum level of TGF-β1 was specifically higher in patients with CAD than in healthy controls. Serum levels of active TGF-β1 can be used to effectively distinguish CAD patients from healthy controls. TGF-β1 overexpression promoted the apoptosis of HCAEC and TGF-β1 siRNA silencing inhibited the apoptosis of HCAEC. TGF-β1 overexpression also promoted the expression of SPHK1 and TIMP-1. SPHK1 overexpression upregulated TIMP-1 but it showed no significant effects on TGF-β1. TIMP-1 overexpression showed no significant effects on TGF-β1 or SPHK1. SPHK1 inhibitor and TIMP-1 silencing reduced the enhancing effects of TGF-β1 overexpression on cell apoptosis.
Conclusions
TGF-β1 appears to promote CAD through the induction of cell apoptosis by upregulating SPHK1 expression and further upregulating its downstream TIMP-1.
... This observation led to the development of some diagnostic approaches for "multimarker" analysis so that the specificity and sensitivity of detection can be increased and/or improved. [21][22][23][24][25][26][27][28][29][30][31][32][33][34][35] Clinical biomarkers By extracting and refining the literature over the last decade, it was found that most of the clinical biomarkers being investigated are proteins in nature, some of them are demonstrated in Table 1 shows examples of the recently-investigated clinical biomarkers which can be potentially used in the detection of early stages of DN or in the monitoring of DN in some situations. The study stated that the expression of SOD-1 was reduced in streptozotocin (STZ)-induced rats in comparison to normal rats. ...
... There was no correlation between the TGF-β1 serum concentration and the expression of TGF-β1 receptor on lens capsule. In humans, elevated serum TGF-β1 were found in diabetic patients (Jakuš et al., 2012;Mou et al., 2016). As far as we know no study about serum TGF-β1in diabetic dogs exist. ...
Tissue fibrosis as complication of diabetes mellitus is known in humans. Because TGF-β1induces fibrosis and is elevated in humans suffering from diabetes mellitus we measured this growth factor in serum of dogs with diabetes mellitus and compared it with healthy dogs and those with fibrotic diseases. Further we measured the expression of TGF-β1receptor on lens capsule to investigate possible association between diabetes mellitus and cataract associated alterations. TGF-β1 was measured in serum of 12 dogs with diabetes mellitus, 20 healthy controls and 12 dogs with fibrotic diseases. Dogs with diabetes mellitus and fibrotic diseases have significantly increased TGF-β1 serum concentrations compared to healthy controls. Some dogs with diabetes mellitus showed increased expression of TGF-β1 receptor in lens capsule. Based on our observations we can conclude that TGF-β1 elevation in dogs with diabetes mellitus may induces complications of the disease and may participates on lens alteration.
