scholarly journals HUBUNGAN ANTARA KADAR TGF-Β1 DENGAN KADAR ALBUMIN DALAM URIN PASIEN DM TIPE-2 DENGAN NEFROPATI DIABETIK

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


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. 


e-CliniC ◽  
2017 ◽  
Vol 5 (2) ◽  
Author(s):  
. Yuswanto ◽  
Emma S. Moeis ◽  
Maarthen C.P. Wongkar

Abstract: Smoking can augment the risk for kidney disease by increasing the expression of Transforming Growth Factor-β1 (TGF-β1) in the kidneys (uTGF-β1). Early glomerular dysfunction in smokers can be evaluated by measuring albuminuria (urine albumin-to-creatinine ratio/uACR), which generally appears before a decrease in estimated glomerular filtration rate (eGFR). This study was aimed to determine the relationship between smoking and the level of eGFR through changes in levels of uTGF-β1 and uACR among male smokers compared to non-smokers. This was an observational analytical study with a cross-sectional design conducted at Pineleng Subdistrict, Manado. Subjects of this study were 80 males (40 smokers and 40 non-smokers). The results showed significant differences in levels of uTGF-β1 and uACR among smokers compared to non-smokers (P values 0.003 and 0.012). The correlation test showed significant correlations between the increase in uACR levels and the decrease in eGFR levels (P = 0.019), as well as the duration of smoking and the increase in uTGF-β1 levels (P = 0.000). There was no significant association (P = 0.470) between smoking and the risk of decreased eGFR level (PR = 0.704). Therefore, smoking cannot be used as a predictor of eGFR decline. Conclusion: There were no correlations between uTGF-β1 and uACR as well as uTGF-β1 and eLFG.Keywords: Urine Transforming Growth Factor-β1, uACR, GFR, smokersAbstrak: Merokok dapat meningkatkan risiko penyakit ginjal melalui peningkatan ekspresi Transforming Growth Factor-β1 (TGF-β1) pada ginjal (uTGF-β1). Gangguan glomerular dini pada perokok dapat dievaluasi dengan pengukuran albuminuria (rasio albumin kreatinin urin/RAKU), yang umumnya muncul sebelum terjadi penurunan estimasi laju filtrasi glomerulus (eLFG). Penelitian ini bertujuan untuk mengetahui hubungan merokok dengan nilai eLFG melalui perubahan kadar uTGF-β1 dan RAKU pada pria perokok dibanding non-perokok. Jenis penelitian ialah observasional analitik dengan desain potong lintang yang dilaksanakan di Kecamatan Pineleng, Manado. Subyek penelitian yaitu 80 pria (40 perokok dan 40 non-perokok). Hasil penelitian menunjukkan perbedaan bermakna kadar uTGF-β1 dan RAKU antara perokok dibanding non-perokok (P = 0,003 dan 0,012). Terdapat hubungan bermakna (P = 0,470) antara merokok dan risiko penurunan eLFG (PR = 0,704). Tidak terdapat perbedaan eLFG antara subyek perokok dan non-perokok. Tidak terdapat hubungan antara kadar uTGF-β1 dan RAKU. Tidak terdapat hubungan antara kadar uTGF-β1 dan nilai eLFG. Terdapat hubungan bermakna antara lama merokok dan peningkatan kadar uTGF-β1, namun tidak terdapat hubungan antara lama merokok dengan RAKU dan nilai eLFG. Peningkatan RAKU pada perokok berkorelasi dengan peningkatan nilai eLFG. Karena itu merokok tidak dapat digunakan sebagai prediktor penurunan eLFG. Simpulan: Tidak terdapat hubungan antara kadar uTGF-β1 baik dengan RAKU maupun nilai eLFG.Kata kunci: Urine Transforming Growth Factor-β1, RAKU, LFG, perokok


2006 ◽  
Vol 190 (1) ◽  
pp. 141-150 ◽  
Author(s):  
Sílvia Emiko Matsuo ◽  
Suzana Garcia Leoni ◽  
Alison Colquhoun ◽  
Edna Teruko Kimura

Transforming growth factor-beta 1 (TGF-β1) and activin A (ActA) induce similar intracellular signaling mediated by the mothers against decapentaplegic homolog (SMAD) proteins. TGF-β1 is a potent antimitogenic factor for thyroid follicular cells, while the role of ActA is not clear. In our study, the proliferation of TPC-1, the papillary thyroid carcinoma cell line, was reduced by both recombinant ActA and TGF-β1. Due to the concomitant expression of TGF-β1 and ActA in thyroid tumors, we investigated the effects of either TGF-β1 or ActA gene silencing by RNA interference in TPC-1 cells in order to distinguish the specific participation of each in proliferation and intracellular signaling. An increased proliferation and reduced SMAD2, SMAD3, and SMAD4 mRNA expression were observed in both TGF-β1 and ActA knockdown cells. Recombinant TGF-β1 and ActA increased the expression of inhibitory SMAD7, whereas they reduced c-MYC. Accordingly, we detected a reduction in SMAD7 expression in knockdown cells while, unexpectedly, c-MYC was reduced. Our data indicate that both TGF-β1 and ActA generate SMADs signaling with each regulating the expression of their target genes, SMAD7 and c-MYC. Furthermore, TGF-β1 and ActA have an antiproliferative effect on thyroid papillary carcinoma cell, exerting an important role in the control of thyroid tumorigenesis.


2001 ◽  
Vol 194 (6) ◽  
pp. 809-822 ◽  
Author(s):  
Chun Geun Lee ◽  
Robert J. Homer ◽  
Zhou Zhu ◽  
Sophie Lanone ◽  
Xiaoman Wang ◽  
...  

Interleukin (IL)-13 is a key mediator of tissue fibrosis caused by T helper cell type 2 inflammation. We hypothesized that the fibrogenic effects of IL-13 are mediated by transforming growth factor (TGF)-β. To test this hypothesis we compared the regulation of TGF-β in lungs from wild-type mice and CC10-IL-13 mice in which IL-13 overexpression causes pulmonary fibrosis. IL-13 selectively stimulated TGF-β1 production in transgenic animals and macrophages were the major site of TGF-β1 production and deposition in these tissues. IL-13 also activated TGF-β1 in vivo. This activation was associated with decreased levels of mRNA encoding latent TGF-β–binding protein-1 and increased mRNA encoding urinary plasminogen activator, matrix metalloproteinase (MMP)-9, and CD44. TGF-β1 activation was abrogated by the plasmin/serine protease antagonist aprotinin. It was also decreased in progeny of crosses of CC10-IL-13 mice and MMP-9 null mice but was not altered in crosses with CD44 null animals. IL-13–induced fibrosis was also significantly ameliorated by treatment with the TGF-β antagonist soluble TGFβR-Fc (sTGFβR-Fc). These studies demonstrate that IL-13 is a potent stimulator and activator of TGF-β1 in vivo. They also demonstrate that this activation is mediated by a plasmin/serine protease- and MMP-9–dependent and CD44-independent mechanism(s) and that the fibrogenic effects of IL-13 are mediated, in great extent, by this TGF-β pathway.


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