SO082LATENT TRANSFORMING GROWTH FACTOR BETA BINDING PROTEIN (LTBP4) CAN REGULATE RENAL FIBROSIS AND ALTER INFLAMMATION AND MITOCHONDRIAL DYSFUNCTION IN CHRONIC KIDNEY DISEASE (CKD)

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Chi-Ting Su ◽  
Tzu-Ming Jao ◽  
Jenq-Wen Huang
Keyword(s):  
Chronic Kidney Disease ◽  
Growth Factor ◽  
Kidney Disease ◽  
Transforming Growth Factor Beta ◽  
Culture System ◽  
Transforming Growth Factor ◽  
Renal Tissue ◽  
Macrophage Infiltration ◽  
Tgf Beta ◽  
Growth Factor Beta

Abstract Background and Aims: Transforming growth factor beta (TGF-beta) has been well known as a key factor for fibrosis and inflammation. LTBPs regulate TGF-beta signalling in complicated ways. Disruption and loss of LTBP4 expression is associated with abnormal accumulation of extracellular matrix (ECM) and altered TGF-beta activation. However, the role of LTBP4 in chronic kidney disease remains largely unknown. We aim to explore the mechanisms of LTBP4-related regulation in kidney disease. Method: To investigate the impact of LTBP4 on tubulointeresitial fibrosis (TIF), we generated LTBP4-overexpression human renal proximal tubule cells (HK-2), treated with exogenous TGF-beta and established a fibroblasts-HK-2 co-culture system using rat fibroblasts (NRK-49F) and HK-2 cells. Moreover, to create TIF model, we performed unilateral ureteral ligation (UUO) in Ltbp4S-/- mice and wild-type (WT) mice to check ECM deposition and phenotypic alterations. In addition, we performed RNA-Sequencing analysis to understand transcriptomic changes associate with LTBP4 overexpression. Results: Up-regulation of Ltbp4 in fibrotic kidney was noted in TIF model with UUO and in renal tissue with diabetic nephropathy. LTBP4-overexpression reduced epithelial-mesenchymal transition (EMT) with showing increased epithelial-cadherin, reduced vimentin and collagen I in the co-culture system. Moreover, higher expression of fibronectin, collagen I and alpha-smooth muscle actin (alpha-SMA) were noted in fibrotic kidneys in Ltbp4S-/- mice compared with changes in WT mice, suggesting inflammation condition could be altered by the absence of Ltbp4S. The inflammatory change in renal tissue in UUO model was studied with F4/80 stain. Increased macrophage infiltration and increased monocyte chemoattractant protein-1 (MCP-1) expression were detected in Ltbp4S-/- mice compared with that in WT mice. In addition, LTBP4-overexpression reduced mitochondrial biogenesis. Conclusion: Ltbp4 acted as a regulator of fibrosis and inflammation in fibrotic kidneys. TGF-beta- induced EMT were clearly enhanced in ltbp4 deficient environments, accompanied with reduced macrophage infiltration, which could be the major mechanism related to LTBP4/TGF-beta pathways. Furthermore, altered ATP production and usage as well as mitochondria respiration could be regulated by LTBP4 in renal failure.

scholarly journals MicroRNA in kidney disease

2016 ◽  
Vol 14 (1) ◽  
pp. 8-10 ◽  
Author(s):  
Ingrid Prkacin ◽  
Gordana Cavric ◽  
Nikolina Basic-Jukic
Keyword(s):  
Chronic Kidney Disease ◽  
Growth Factor ◽  
Kidney Disease ◽  
Transforming Growth Factor Beta ◽  
Kidney Development ◽  
Transforming Growth Factor ◽  
Therapeutic Potential ◽  
Kidney Diseases ◽  
Kidney Fibrosis ◽  
Growth Factor Beta

AbstractClinical and laboratory findings of kidney disease in an adult may find an explanation in kidney functional and/or structural abnormalities that already existed during infancy and childhood, but that may have been missed or underdiagnosed. All the cardiovascular abnormalities that occur in adults with chronic kidney disease are also present in children with chronic kidney disease. Complications in childhood chronic kidney disease will have consequences well beyond pediatric age and influence outcomes of affected young adults with disease. Kidney dysfunction appears early in the course of kidney disease and has been observed in children and adults with chronic kidney disease, condition characterised with kidney fibrosis. Transforming growth factor beta is recognized as a major mediator of kidney fibrosis. New evidence illustrates the relationship between transforming growth factor beta signaling and microRNAs expression during kidney diseases development. MicroRNAs play important roles in kidney development and kidney diseases; they are naturally occurring, 22-nucleotide, noncoding RNAs that mediate posttranscriptional gene regulation. Dysregulation of miRNA expression is an indicator of several diseases including chronic kidney disease. Targeting microRNAs should be a therapeutic potential to ameliorate the disease related to fibrosis. The discovery that circulating miRNAs are detectable in serum and plasma, and that their expression varies as a result of disease, presents great potential to be used as biomarkers in kidney disease prevention and diagnosis.

The Association between Biomarker Profiles, Etiology of Chronic Kidney Disease, and Mortality

2017 ◽  
Vol 45 (3) ◽  
pp. 226-234 ◽  
Author(s):  
David Langsford ◽  
Mila Tang ◽  
Hicham I. Cheikh Hassan ◽  
Ognjenka Djurdjev ◽  
Manish M. Sood ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Growth Factor ◽  
Kidney Disease ◽  
Transforming Growth Factor Beta ◽  
Troponin I ◽  
Transforming Growth Factor ◽  
Fibroblast Growth Factor 23 ◽  
High Sensitivity ◽  
Adverse Outcomes ◽  
Growth Factor Beta

Background: Prognosis in chronic kidney disease (CKD) for adverse outcomes differs substantially based on the etiology of CKD. We examined whether the biomarker profile differed based on CKD etiology and whether they were associated with mortality. Methods: Prospective observational study of 1,157 patients, 663 with diabetic kidney disease (DKD), 273 with glomerulonephritis (GN), and 221 with cystic/interstitial disease (polycystic kidney disease, pyelonephritis or chronic tubulointerstitial nephritis [PCK/TIN]) were identified in the Canadian Study of Prediction of Dialysis, Death and Interim Cardiovascular events over Time cohort. The outcome of interest was mortality before commencing dialysis. The biomarker profile consisted of N-terminal pro-brain natriuretic peptide (NT-proBNP), troponin I (TnI), asymmetric dimethylarginine (ADMA), interleukin (IL)-6, high sensitivity C-reactive protein, fibroblast growth factor-23 (FGF23), transforming growth factor-beta, 25-hydroxylvitamin D, and cystatin C (CysC). Results: The mean estimated glomerular filtration rate was 27 mL/min/1.73 m2 and median follow-up time was 44 months. Mortality before dialysis commencement was the greatest in DKD (20%), followed by PCK/TIN (13%), and was least in those GN (8%). The majority of deaths were cardiovascular in nature, 17, 9, and 5.5% for DKD, PCK/TIN, GN, respectively. Those with DKD had higher hazard for mortality, unadjusted (hazard ratio [HR] 2.7, 95% CI 1.7-4.3) and adjusted (HR 1.7, 95% CI 1.1-2.8). The biomarker profiles associated with mortality differed significantly by CKD etiology as follows: DKD was associated with CysC (HR 1.3, 95% CI 1.0-1.6), ADMA (HR 1.3, 95% CI 1.1-1.6), and NT-proBNP (HR 1.7, 95% CI 1.4-2.1), GN was associated with FGF23 (HR 1.8, 95% CI 1.1-2.8), TnI (HR 3.6, 95% CI 1.3-9.5), and transforming growth factor-beta (HR 0.6, 95% CI 0.4-0.9) and PCK/TIN was associated with ADMA (HR 1.5, 95% CI 1.3-1.8) and IL-6 (HR 2.1, 95% CI 1.5-3.1). Conclusions: Biomarkers profiles differ according to the etiology of CKD and are associated with mortality.

scholarly journals Phenotypic modulation of endothelial cells by transforming growth factor-beta depends upon the composition and organization of the extracellular matrix.

1988 ◽  
Vol 106 (4) ◽  
pp. 1375-1384 ◽  
Author(s):  
J A Madri ◽  
B M Pratt ◽  
A M Tucker
Keyword(s):  
Cell Proliferation ◽  
Endothelial Cells ◽  
Growth Factor ◽  
Transforming Growth Factor Beta ◽  
Culture System ◽  
Transforming Growth Factor ◽  
Inhibitory Effect ◽  
Endothelial Cell Proliferation ◽  
Tgf Beta ◽  
Growth Factor Beta

Transforming growth factor beta (TGF-beta) is angiogenic in vivo. In vitro, endothelial cell proliferation is inhibited by TGF-beta. We have correlated this inhibitory effect with an increase in cellular fibronectin synthesis and deposition in a two-dimensional culture system using specific matrix coatings. The inhibitory effect was mimicked by addition of soluble fibronectin to cultures. In contrast, TGF-beta was found to elicit the formation of tube-like structures (mimicking angiogenesis) when microvascular endothelial cells were grown in three-dimensional collagen gels. In this culture system TGF-beta elicited rapid extensive formation of complex, branching, tube-like structures, while cell proliferation was not inhibited. These data confirm and support the hypothesis that TGF-beta is angiogenic and may exert some of its effects through modulation of matrix synthesis and are consistent with the hypothesis that the organization of the extracellular environment influences cellular responses to this "panregulin."

scholarly journals Evaluating the Serum Transforming Growth Factor-Beta 1 Level in Chronic Kidney Disease Caused by Glomerulonephritis

2021 ◽  
Vol In Press (In Press) ◽  
Author(s):  
Tuan Van Nguyen ◽  
Ky Duc Ngo ◽  
Minh Hoang Thi ◽  
Lan Thi Phuong Dam ◽  
Thuan Quang Huynh
Keyword(s):  
Chronic Kidney Disease ◽  
Growth Factor ◽  
Kidney Disease ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Healthy Control Group ◽  
Control Group ◽  
Healthy Control ◽  
Growth Factor Beta ◽  
Tgf Β1

Background: The transforming growth factor-beta 1 (TGF-β1) has been demonstrated as one of the main factors in the progression of fibrosis and sclerosis glomerular damages. Glomerulonephritis is one common cause of chronic kidney disease (CKD) with the promotion of inflammatory renal damage containing fibrosis and sclerosis glomerular. Objectives: This study aimed to evaluate the TGF-β1 level in CKD patients and compare it with the healthy control group. Methods: This cross-sectional case-control study was carried out on 212 subjects admitted to the Nghe An Friendship General Hospital in Vietnam from March 2018 to February 2020. The case group included 152 patients diagnosed with CKD caused by glomerulonephritis, and the control group included 60 healthy individuals. The TGF-β1 was determined in serum by ELISA method. Results: The serum TGF-β1 concentration of the healthy control group and CKD group was 13.45 ± 7.17 and 32.35 ± 11.74, respectively. The CKD group had a significantly higher TGF-β1 level than the control group (P < 0.05). The CKD group with the eGRP ≥ 60 mL/min/1.73 m2 group had a higher TGF-β1 level than the eGRP < 60 mL/min/1.73 m2 group, and the TGF-β1 level increased from stage 1 to stage 5 (P < 0.001). The TGF-β1 had a medium correlation to urea, creatinine, and hs-CRP. Conclusions: The concentration of TGF-β1 in the CKD group was higher than the control group so that it increased early from the first stage of the disease.

scholarly journals Identification of a novel transforming growth factor-beta (TGF-beta 5) mRNA in Xenopus laevis.

1990 ◽  
Vol 265 (2) ◽  
pp. 1089-1093 ◽  
Author(s):  
P Kondaiah ◽  
M J Sands ◽  
J M Smith ◽  
A Fields ◽  
A B Roberts ◽  
...  
Keyword(s):  
Growth Factor ◽  
Xenopus Laevis ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Tgf Beta ◽  
Growth Factor Beta

scholarly journals Recombinant type 1 transforming growth factor beta precursor produced in Chinese hamster ovary cells is glycosylated and phosphorylated.

1988 ◽  
Vol 8 (5) ◽  
pp. 2229-2232 ◽  
Author(s):  
A M Brunner ◽  
L E Gentry ◽  
J A Cooper ◽  
A F Purchio
Keyword(s):  
Growth Factor ◽  
Transforming Growth Factor Beta ◽  
Chinese Hamster Ovary ◽  
Transforming Growth Factor ◽  
Chinese Hamster Ovary Cells ◽  
Chinese Hamster ◽  
Tgf Beta ◽  
Ovary Cells ◽  
Growth Factor Beta

Analyses of cDNA clones coding for simian type 1 transforming growth factor beta (TGF-beta 1) suggest that there are three potential sites for N-linked glycosylation located in the amino terminus of the precursor region. Analysis of [3H]glucosamine-labeled serum-free supernatants from a line of Chinese hamster ovary cells which secrete high levels of recombinant TGF-beta 1 indicate that the TGF-beta 1 precursor, but not the mature form, is glycosylated. Digestion with neuraminidase resulted in a shift in migration of the two TGF-beta 1 precursor bands, which suggests that they contain sialic acid residues. Endoglycosidase H had no noticeable effect. Treatment with N-glycanase produced two faster-migrating sharp bands, the largest of which had a molecular weight of 39 kilodaltons. TGF-beta 1-specific transcripts produced by SP6 polymerase programmed the synthesis of a 42-kilodalton polypeptide which, we suggest, is the unmodified protein backbone of the precursor. Labeling with 32Pi showed that the TGF-beta 1 precursor was phosphorylated in the amino portion of the molecule.

scholarly journals Transforming growth factor beta suppresses human immunodeficiency virus expression and replication in infected cells of the monocyte/macrophage lineage.

1991 ◽  
Vol 173 (3) ◽  
pp. 589-597 ◽  
Author(s):  
G Poli ◽  
A L Kinter ◽  
J S Justement ◽  
P Bressler ◽  
J H Kehrl ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
T Cell ◽  
Growth Factor ◽  
Cell Line ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Tgf Beta ◽  
Immunodeficiency Virus ◽  
Growth Factor Beta

The pleiotropic immunoregulatory cytokine transforming growth factor beta (TGF-beta) potently suppresses production of the human immunodeficiency virus (HIV), the causative agent of the acquired immunodeficiency syndrome, in the chronically infected promonocytic cell line U1. TGF-beta significantly (50-90%) inhibited HIV reverse transcriptase production and synthesis of viral proteins in U1 cells stimulated with phorbol myristate acetate (PMA) or interleukin 6 (IL-6). Furthermore, TGF-beta suppressed PMA induction of HIV transcription in U1 cells. In contrast, TGF-beta did not significantly affect the expression of HIV induced by tumor necrosis factor alpha (TNF-alpha). These suppressive effects were not mediated via the induction of interferon alpha (IFN-alpha). TGF-beta also suppressed HIV replication in primary monocyte-derived macrophages infected in vitro, both in the absence of exogenous cytokines and in IL-6-stimulated cultures. In contrast, no significant effects of TGF-beta were observed in either a chronically infected T cell line (ACH-2) or in primary T cell blasts infected in vitro. Therefore, TGF-beta may play a potentially important role as a negative regulator of HIV expression in infected monocytes or tissue macrophages in infected individuals.

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