Serum TGF-β1 as a Biomarker for Type 2 Diabetic Nephropathy: A Meta-Analysis of Randomized Controlled Trials

Mou, Xin; Zhou, Daohong; Zhou, Danyang; Ma, Jinjin; Liu, Yinghui; Chen, Huiping; Hu, Yongbin; Shou, Chengchao; Chen, Jiawei; Liu, Wenhong; Ma, Guo-ling

doi:10.1371/journal.pone.0149513

Cited by 35 publications

(23 citation statements)

References 21 publications

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“…Consistent with a previous report [50], the penile cross-sectional area (%) was decreased in DM mice, resulting in atrophy of the penis. The increase of collagen fibers in the testis of animals with DM 72 Day A may have been caused by increased expression of transforming growth factor beta 1 and nitric oxide synthase [51][52][53][54]. Similar to our study, previous studies have demonstrated decreases of sperm concentration in DM human and animal models [5,6,37,42,[55][56][57][58], which may be due to impaired spermatogenesis [5,6,12,57,[59][60][61].…”

Section: Discussionsupporting

confidence: 85%

Comparison of male reproductive parameters in mice with type 1 and type 2 diabetes

Sampannang

Arun

Burawat

et al. 2020

Clin Exp Reprod Med

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Objective: The differences between type 1 and type 2 diabetes mellitus (T1DM and T2DM) in terms of their adverse effects on male reproductive parameters have never been elucidated. This study aimed to distinguish between the effects of the DM types in mice treated with multiple low doses of streptozotocin (STZ) to mimic human T1DM and coadministered a high-fat diet (HFD) to mimic human T2DM.Methods: The T1DM mice were intraperitoneally injected with STZ (40 mg/kg body weight) for 5 days. The T2DM mice received an HFD for 14 days prior to STZ injection (85 mg/kg body weight), followed by continuous feeding of an HFD. Male reproductive parameters were evaluated.Results: The reproductive organs of the DM mice weighed significantly less than those of controls, and the seminal vesicles plus prostates of the T1DM mice weighed less than those of the T2DM mice. Increased sperm abnormalities and incomplete DNA packaging were observed in the DM groups. Sperm concentration and the proportion of normal sperm were significantly lower in the T1DM group. The seminiferous histopathology of DM mice was classified into seven types. The penises of the DM mice were smaller than those of the controls; however, tunica albuginea thickness and the amount of penile collagen fibers were increased in these mice. Round germ cells were abundant in the epididymal lumens of the mice with DM.Conclusion: T1DM adversely affected reproductive parameters to a greater extent than T2DM.

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Section: Discussionsupporting

confidence: 85%

Comparison of male reproductive parameters in mice with type 1 and type 2 diabetes

Sampannang

Arun

Burawat

et al. 2020

Clin Exp Reprod Med

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“…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.…”

Section: Discussionmentioning

confidence: 99%

Relationship between transforming growth factor-β1 and type 2 diabetic nephropathy risk in Chinese population

Zhou

Zhong

et al. 2018

BMC Med Genet

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BackgroundDiabetes 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.MethodsAssociation 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.ResultsForty-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).ConclusionsHigh 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.

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“…Increased expression level of TGF-β1 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-β1 levels were significantly higher in patients with diabetic nephropathy than those in healthy controls, and the increased TGF-β1 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-β1 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 ].…”

Section: Discussionmentioning

confidence: 99%

Transforming Growth Factor β1 (TGF-β1) Appears to Promote Coronary Artery Disease by Upregulating Sphingosine Kinase 1 (SPHK1) and Further Upregulating Its Downstream TIMP-1

et al. 2018

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BackgroundTransforming 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/MethodsA 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.ResultsSerum 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.ConclusionsTGF-β1 appears to promote CAD through the induction of cell apoptosis by upregulating SPHK1 expression and further upregulating its downstream TIMP-1.

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Serum TGF-β1 as a Biomarker for Type 2 Diabetic Nephropathy: A Meta-Analysis of Randomized Controlled Trials

Cited by 35 publications

References 21 publications

Comparison of male reproductive parameters in mice with type 1 and type 2 diabetes

Comparison of male reproductive parameters in mice with type 1 and type 2 diabetes

Relationship between transforming growth factor-β1 and type 2 diabetic nephropathy risk in Chinese population

Transforming Growth Factor β1 (TGF-β1) Appears to Promote Coronary Artery Disease by Upregulating Sphingosine Kinase 1 (SPHK1) and Further Upregulating Its Downstream TIMP-1

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