scholarly journals Vitamin D in Different Stages of Type 2 Diabetic Nephropathy and its Correlation with Transforming Growth Factor Beta-1 (TGF-β1) –A Cross Sectional Study

Author(s):  
Liji Kavuparambil ◽  
Ashok Kumar Pammi ◽  
T. K. Jithesh ◽  
K. Shifa

Background: Diabetic nephropathy (DN) is a microvascular complication of Diabetes Mellitus (DM) and the prevalence of which is increasing in every year. Monitoring of Vitamin D status in diabetic nephropathy patients is important, as the deficiency of vitamin D appears as a risk factor for the development of diabetic nephropathy. Studies evaluating the role of vitamin D in DN are few. Conflicting data is available on the correlation between vitamin D and Diabetic Nephropathy. Studies revealed the sample population is Vitamin D deficient. Therefore, it is important to understand the correlation of Vitamin D with severity of Diabetic nephropathy and its role in fibrogenesis. The aim of this study is to analyse vitamin D status in different stages of type 2 diabetic nephropathy and its correlation with transforming growth factor beta-1. Methods: A 1.5-year cross-sectional study of 120 diabetic patients, 60 with nephropathy and 60 without nephropathy patients enrolled to MES Medical College. Patients with heart, liver, or thyroid disease, as well as those on dialysis, were excluded from the study. The VITROS 5600 integrated system were used to measure fasting blood sugar (FBS), HbA1c, creatinine and vitamin D.  Transforming Growth Factor Beta-1 (TGF-β1) is measured using ELISA technique. According to HbA1c and estimated glomerular filtration rate (eGFR) values, the study population is divided into two groups. The statistical package for the social sciences (SPSS) software was used to conduct the analysis. The level of significance was calculated at 95%. Results: The level of vitamin D in diabetic patients with nephropathy is much lower than in diabetic patients without nephropathy. In diabetic nephropathy patients, serum creatinine, urea, HbA1c and TGF-β1 exhibited a highly significant negative correlation with vitamin D status, but eGFR showed a highly significant positive correlation. Conclusion: Vitamin D status has been found to be poor in all diabetic patients, with a greater drop in diabetic nephropathy patients. In diabetic nephropathy patients, serum creatinine, urea, HbA1c and TGF-β1 exhibited a highly significant negative association with vitamin D status, but eGFR showed a highly significant positive link. Deficiency of vitamin D have role in the development and severity of DN, and showed a highly significant correlation with the regulator of fibrosis, TGF-β1. This finding indicates that vitamin D couldbe an important factor for development and progression of Diabetic nephropathy. So supplementation of vitamin D may slow down progression of DN. 

2019 ◽  
Vol 7 (1) ◽  
pp. 73-81
Author(s):  
Elfiani Elfiani ◽  
Rita Halim ◽  
M Haldian Hakir

ABSTRACT Background: Diabetic nephropathy (DN) is a complication of diabetes in the kidney that frequently causes terminal kidney disease. This kidney disease caused by diabetes is a syndrome characterized by albumin in urine (albuminuria). Growth factor-β1 (TGF- β1) is a multifunctional cytokine that controls many biological processes, including immunity, differentiation, tumor suppression, tumor metastasis, aging, migration, wound healing, apoptosis, adipogenesis, and osteogenesis. Previous studies had showed that TGF-β1 plays a role in albuminuria, where TGF-β1 expression in the kidney increases in diabetes patients. Elevation of cytokine level, especially transforming growth factor beta-1 (TGF-β1) that induces the increase of several extra cellular matrices (ECM), i.e. fibronectin, integrin-linked kinase (ILK) and type IV collagen. This TGF-β1 activity causes the accumulation of ECM, which leads to thickened glomerular basement membrane (GBM). Thickening of GBM and changes in kidney structure in the form of hypertrophy and reduced glomerular podocytes caused by apoptosis and attachment in GBM causes protein components to exit through urine (albuminuria). This study aimed to prove the correlation between transforming growth factor-β1 and albumin level in urine of diabetic nephropathy. Metode : This study a observasional with desain Cross-sectional  comparative study. Results: Mean TGF-β1 level in type 2 DM patients with diabetic nephropathy in this study was 47.30 ± 14.70 ng/ml, with similar value between men and women with 43.1 ng/ml and 44.7 ng/ml, respectively. Out of 60 type 2 DM participants with ND, the mean albuminuria level according to ACR was 722.53 ± 1854.96 mg/g. The result of male participants was lower compared to female participants, with 667.8 mg/mg and 777.2 mg/g, respectively. Conclusion: There was insignificant correlation between TGF-β1 in diabetic nephropathy (DN) and albumin level in urine measured using albumin and urine creatinine ratio (ACR) (p = 0.066). Keywords: Diabetic Nephropathy, Albuminuria, TGF-β1   ABSTRAK Latar Belakang : Nefropati diabetik (ND) merupakan komplikasi diabetes pada ginjal yang paling sering menyebabkan terjadinya penyakit ginjal terminal. Penyakit ginjal akibat diabetes ini merupakan sindroma dengan karakteristik terdapatnya albumin dalam urine (albuminuria). Faktor pertumbuhan-β1 (TGF-β1) adalah sebuah sitokin multifungsi yang mengendalikan banyak proses biologis termasuk kekebalan, diferensiasi, tumor supresi, tumor metastasis, penuaan, migrasi, penyembuhan luka, apoptosis, adipogenesis, dan osteogenesis. Sejumlah penelitian sebelumnya menunjukkan bahwa TGF-β1 berperan terhadap terjadinya albuminuria, dimana pasien diabetes didapatkan ekspresi TGF-β1 di ginjal meningkat. Peningkatan kadar cytokine terutama Transforming Growth Factor Beta-1 (TGF-β1) yang menginduksi peningkatan beberapa Extra Cellular Matrix (ECM) antara lain fibronectin, integrin-linked kinase (ILK) dan collagen tipe-IV. Aktifitas TGF-β1 ini menyebabkan akumulasi ECM sehingga terjadi penebalan Glomerular Basement Membrane (GBM). Penebalan dari GBM dan terjadinya perubahan struktur ginjal berupa hipertrofi dan berkurangnya sel-sel podocyte glomerulus akibat kerusakan (apoptosis) dan perlengketan di GBM menyebabkan komponen protein keluar melalui urin (albuminuria). Tujuan penelitian ini untuk membuktikan hubungan antara kadar transforming growth  factor-β1 dengan kadar albumin dalam urin pada Nefropati Diabetik. Metode : Penelitian ini merupakan penelitian Observasional dengan desain Cross-sectional   comparative study. Hasil : Kadar rata-rata TGF-β1 pasien DM tipe-2 dengan Nefropati Diabetik pada penelitian ini adalah 47,30 ± 14,70 ng/ml, tidak jauh berbeda antara laki-laki yaitu 43,1 ng/ml dengan perempuan 44,7 ng/ml. Dari 60 orang responden DM tipe-2 dengan ND pada penelitian ini didapatkan kadar albuminuria rata-rata berdasarkan ACR adalah 722,53 ± 1854,96 mg/g. Responden laki-laki lebih rendah dibanding perempuan yaitu 667,8 mg/g berbanding 777,2 mg/g. Kesimpulan : Tidak terdapat hubungan yang bermakna antara TGF-β1 pada Nefropati Diabetik (ND) dengan kadar albumin dalam urin yang dihitung berdasarkan rasio albumin dan creatinin urin (ACR) (p=0,066). Kata Kunci : Nefropati Diabetik, Albuminuria, TGF-β1


Author(s):  
Alvilusia Alvilusia ◽  
Amir Fauzi ◽  
Azhari Azhari ◽  
Wresnindyatsih Wresnindyatsih ◽  
Irsan Saleh

Objective: To know the correlation of the expression of transforming growth factor beta (TGF-β1) and tropoelastin in uterine prolapse. Method: A cross-sectional study of 30 subjects suffered from uterine prolapse in the Department of Obstetrics and Gynecology Dr. Mohammad Hoesin hospital Palembang. The study was conducted since December 1st, 2014 until July 31st, 2015. The sample was from the sacrouterine ligament and immunohistochemical examination was conducted to see the expression of TGF-β1 and tropoelastin. Result: Of the 30 subjects obtained, the expression of TGF-β1 was on 30 subjects consisting of 18 (60%) for weak expression and 12 (40%) for strong expression. Meanwhile, the strong tropoelastin expression was on 18 subjects (60%) and weak tropoelastin expression on 12 subjects (40%). There was a positive correlation between TGF-β1 and tropoelastin expression with moderate correlation (p=0.014; r=0.44). Conclusion: There is a positive correlation between the TGF-β1 and tropoelastin expression of sacrouterine ligament in uterine prolapse with moderate correlation. [Indones J Obstet Gynecol 2016; 4-2: 70-74] Keywords: transforming Growth Factor Beta 1, tropoelastin, uterine prolapse


2004 ◽  
Vol 19 (3) ◽  
pp. 236-239 ◽  
Author(s):  
A. Lebrecht ◽  
C. Grimm ◽  
G. Euller ◽  
E. Ludwig ◽  
E. Ulbrich ◽  
...  

Transforming growth factor beta (TGF-β)1 is thought to be involved in breast carcinogenesis. TGF-β1 acts in an antiproliferative manner in the early stages of breast carcinogenesis, but promotes tumor progression and metastases in the advanced stages of the disease. No data have been published on serum TGF-β1 in breast cancer. We investigated TGF-β1 serum levels in patients with breast cancer (n=135), ductal carcinoma in situ (DCIS) I to III (n=67) or fibroadenoma (n=35), and in healthy women (n=40) to determine its value as a differentiation marker between malignant, pre-invasive and benign diseases and as a predictive marker for metastatic spread. Median (range) TGF-β1 serum levels in patients with breast cancer, DCIS I-III or benign breast lesions and in healthy women were 48.8 (18–82.4) pg/mL, 45.3 (26.9–58.3) pg/mL, 47.2 (17.2–80.5) pg/mL and 51.6 (30.9–65.1) pg/mL, respectively (p=0.2). In breast cancer patients TGF-β1 serum levels showed no statistically significant correlation with tumor stage, lymph node involvement, histological grade, estrogen receptor status and progesterone receptor status. Our data fail to indicate any correlation between serum TGF-β1 levels and clinicopathological parameters of breast diseases. Serum TGF-β1 levels do not provide clinical information in addition to established tumor markers.


2018 ◽  
Vol 243 (7) ◽  
pp. 601-612 ◽  
Author(s):  
Nathan Cho ◽  
Shadi E Razipour ◽  
Megan L McCain

Cardiac fibroblasts and their activated derivatives, myofibroblasts, play a critical role in wound healing after myocardial injury and often contribute to long-term pathological outcomes, such as excessive fibrosis. Thus, defining the microenvironmental factors that regulate the phenotype of cardiac fibroblasts and myofibroblasts could lead to new therapeutic strategies. Both chemical and biomechanical cues have previously been shown to induce myofibroblast differentiation in many organs and species. For example, transforming growth factor beta 1, a cytokine secreted by neutrophils, and rigid extracellular matrix environments have both been shown to promote differentiation. However, the relative contributions of transforming growth factor beta 1 and extracellular matrix rigidity, two hallmark cues in many pathological myocardial microenvironments, to the phenotype of human cardiac fibroblasts are unclear. We hypothesized that transforming growth factor beta 1 and rigid extracellular matrix environments would potentially have a synergistic effect on the differentiation of human cardiac fibroblasts to myofibroblasts. To test this, we seeded primary human adult cardiac fibroblasts onto coverslips coated with polydimethylsiloxane of various elastic moduli, introduced transforming growth factor beta 1, and longitudinally quantified cell phenotype by measuring expression of α-smooth muscle actin, the most robust indicator of myofibroblasts. Our data indicate that, although extracellular matrix rigidity influenced differentiation after one day of transforming growth factor beta 1 treatment, ultimately transforming growth factor beta 1 superseded extracellular matrix rigidity as the primary regulator of myofibroblast differentiation. We also measured expression of POSTN, FAP, and FSP1, proposed secondary indicators of fibroblast/myofibroblast phenotypes. Although these genes partially trended with α-smooth muscle actin expression, they were relatively inconsistent. Finally, we demonstrated that activated myofibroblasts incompletely revert to a fibroblast phenotype after they are re-plated onto new surfaces without transforming growth factor beta 1, suggesting differentiation is partially reversible. Our results provide new insights into how microenvironmental cues affect human cardiac fibroblast differentiation in the context of myocardial pathology, which is important for identifying effective therapeutic targets and dictating supporting cell phenotypes for engineered human cardiac disease models. Impact statement Heart disease is the leading cause of death worldwide. Many forms of heart disease are associated with fibrosis, which increases extracellular matrix (ECM) rigidity and compromises cardiac output. Fibrotic tissue is synthesized primarily by myofibroblasts differentiated from fibroblasts. Thus, defining the cues that regulate myofibroblast differentiation is important for understanding the mechanisms of fibrosis. However, previous studies have focused on non-human cardiac fibroblasts and have not tested combinations of chemical and mechanical cues. We tested the effects of TGF-β1, a cytokine secreted by immune cells after injury, and ECM rigidity on the differentiation of human cardiac fibroblasts to myofibroblasts. Our results indicate that differentiation is initially influenced by ECM rigidity, but is ultimately superseded by TGF-β1. This suggests that targeting TGF-β signaling pathways in cardiac fibroblasts may have therapeutic potential for attenuating fibrosis, even in rigid microenvironments. Additionally, our approach can be leveraged to engineer more precise multi-cellular human cardiac tissue models.


2017 ◽  
Vol 9 (1) ◽  
pp. 49 ◽  
Author(s):  
Yusrawati Yusrawati ◽  
Dyka Aidina ◽  
Eti Yerizel

BACKGROUND: According to the theory of endothelial dysfunction, the pathogenesis of preeclampsia is associated with the imbalance of angiogenic and anti-angiogenic factors. Transforming growth factor-beta 1 (TGF-β1) has also proposed as a proangiogenic factor that influences preeclampsia. This study was conducted to compare a mean difference of TGF-β1 between preeclampsia and normal pregnancy.METHODS: This study was an observational crosssectional study with 25 subjects of pregnant women with preeclampsia and 25 subjects of normotensive pregnant women. The study was conducted in Dr. Reksodiwiryo Hospital, Bhayangkara Hospital, and Dr. Rasidin Hospital in Padang, Indonesia from October 2015 to January 2016. For the determination of TGF-β1 concentration, peripheral Abstract venous blood samples were taken. The blood samples wereanalyzed by enzyme-linked immunosorbent assay (ELISA) in Biomedical Laboratory, Faculty of Medicine, Andalas University. The mean difference was statically analyzed by independent samples T-test.RESULTS: The mean difference of TGF-β1 was lower in preeclampsia group than normal pregnancy group (2.02±0.99 ng/mL vs. 3.24±2.67 ng/mL; p<0.05).CONCLUSION: The TGF-β1 concentration was lower in pregnant women with preeclampsia. Thus, it may have a role as a marker in preeclampsia.KEYWORDS: preeclampsia, normal pregnancy, transforming growth factor-beta1, TGF-β1


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