Increased mRNA Expression of Transforming Growth Factor Beta in the Arterial Wall of Chronically Rejected Renal Allografts in Humans

Żegarska, Jolanta; Pączek, Leszek; Pawłowska, Monika; Wyczalkowska, A.; Michalska, W; Ziółkowski, Jerzy; Górski, A; Rowińskí, W; Kosieradzki, Maciej; Kwiatkowski, A.; Górnicka, Barbara; Ziarkiewicz‐Wróblewska, Bogna

doi:10.1016/j.transproceed.2005.12.017

Cited by 7 publications

(6 citation statements)

References 10 publications

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“…The analysis of interaction maps shows also that AKT1 is linked, via IKBKB kinase, to TGF-beta signaling, which is associated to some complications in solid organ recipients, such as post-transplant lymphoproliferative disorder [Babel et al, 2007]. Moreover, TGF-beta pathway mRNA is increased in human kidney chronic rejection [Zegarska et al, 2006]. AKT1 is also linked, via NOS3 (eNOS), to ARG1 and NOS2A.…”

Section: Discussionmentioning

confidence: 99%

AKT1 leader gene and downstream targets are involved in a rat model of kidney allograft tolerance

Jovanović

Giacomelli

Sivozhelezov

et al. 2010

J of Cellular Biochemistry

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Tolerance is the so-called "Holy Grail" of transplantation but achieving this state is proving a major challenge, particularly in the clinical settings. This tolerance state can be induced in rodent models using a variety of maneuvers. This phenomenon is classically characterized by donor specificity (recipients accept a secondary donor-specific allograft but reject third-party allograft) as well as by the absence of chronic rejection lesion. We previously showed that administration and anti-donor anti-class II serum on the day of transplantation induce tolerance to a kidney allograft in the LEW-1W to LEW-1A strain combination. In this study, we used DNA microarrays to compare gene patterns involved in anti-donor anti-class II tolerated or untreated syngeneic kidney transplants in this strain combination. Statistical and non-statistical analyses were combined with ab initio analysis, using the recently developed leader gene approach, to shed new light on this phenomenon. Theoretical and experimental results suggest that tolerance and rejection outcome may be in large part determined by low expression variations of some genes, which can form a core gene network around specific genes such as Rac1, NFKB1, RelA, AKT1, IKBKB, BCL2, BCLX, and CHUK. Through this model, we showed that AKT1 gene, WNT pathway and NO synthesis are strictly connected to each other and may play an important role in kidney tolerance and rejection processes, with AKT1 gene being the center of this complex network of interactions.

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Section: Discussionmentioning

confidence: 99%

AKT1 leader gene and downstream targets are involved in a rat model of kidney allograft tolerance

Jovanović

Giacomelli

Sivozhelezov

et al. 2010

J of Cellular Biochemistry

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“…It also inhibits TGF-β, thus contributing to extracellular matrix turnover, fibrosis, wound healing and tissue repair (Waller and Nicholson 2001), cell growth and proliferation, and anti-inflammatory properties. TGF-β also plays an essential role in the pathogenesis of fibrotic diseases of the kidney, liver, and lung, as well as atherosclerosis, artery remodeling in hypertension and diabetes mellitus, rheumatoid arthritis, and cancer (Harris et al 2007; Zegarska et al 2006; Jain et al 2000; Reinhold et al 1997). Decreased DP-IV expression in the urinary proteome may explain the lack of TGF-β inhibition and indicate a role for DP-IV and TGF-β in the pathogenesis of aging and may explain its reduced ability to regulate the immune system as well as increased susceptibility to type 2 diabetes seen in the elderly (Laudes et al 2010).…”

Section: Discussionmentioning

confidence: 99%

Urine proteomes of healthy aging humans reveal extracellular matrix (ECM) alterations and immune system dysfunction

Bakun

Senatorski

Rubel

et al. 2013

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Aging is a complex physiological process that poses considerable conundrums to rapidly aging societies. For example, the risk of dying from cardiovascular diseases and/or cancer steadily declines for people after their 60s, and other causes of death predominate for seniors older than 80 years of age. Thus, physiological aging presents numerous unanswered questions, particularly with regard to changing metabolic patterns. Urine proteomics analysis is becoming a non-invasive and reproducible diagnostic method. We investigated the urine proteomes in healthy elderly people to determine which metabolic processes were weakened or strengthened in aging humans. Urine samples from 37 healthy volunteers aged 19–90 years (19 men, 18 women) were analyzed for protein expression by liquid chromatography–tandem mass spectrometry. This generated a list of 19 proteins that were differentially expressed in different age groups (young, intermediate, and old age). In particular, the oldest group showed protein changes reflective of altered extracellular matrix turnover and declining immune function, in which changes corresponded to reported changes in cardiovascular tissue remodeling and immune disorders in the elderly. Thus, urinary proteome changes in the elderly appear to reflect the physiological processes of aging and are particularly clearly represented in the circulatory and immune systems. Detailed identification of “protein trails” creates a more global picture of metabolic changes that occur in the elderly.Electronic supplementary materialThe online version of this article (doi:10.1007/s11357-013-9562-7) contains supplementary material, which is available to authorized users.

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“…Publications suggest that TGF‐β 1 regulates the proliferation and migration of SMCs and ECM deposition in CR. Many effects of TGF‐β 1 can be attributed to the activation of ERK [8]. PDGF‐BB is well known to induce TGF‐β 1 expression in VSMCs, which plays a pivotal role in vascular diseases [7].…”

Section: Discussionmentioning

confidence: 99%

“…Moreover, PDGF‐BB induces transforming growth factor‐β 1 (TGF‐β 1 ) expression in VSMCs [7]. Overexpression of TGF‐β 1 , a principal profibrogenetic growth factor that stimulates cell hypertrophy and ECM production, plays a key role in chronic graft fibrosis that generally results from transplant vasculopathy [8]. However, the molecular mechanism of VSMC proliferation, migration and TGF‐β 1 expression induced by PDGF‐BB remains to be fully understood.…”

Section: Introductionmentioning

confidence: 99%

Antisense extracellular signal-regulated kinase-2 gene therapy inhibits platelet-derived growth factor-induced proliferation, migration and transforming growth factor-β₁expression in vascular smooth muscle cells and attenuates transplant vasculopathy

Chen¹,

Chen²,

Ding³

et al. 2007

Transplant Int

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Summary Platelet‐derived growth factor‐BB (PDGF‐BB) enables vascular smooth muscle cells (VSMCs) to proliferate, migrate and secrete connective tissue matrix, which are critical events in transplant vasculopathy. However, little is known about the intracellular pathways that mediate these biologic responses of VSMCs. Extracellular signal‐regulated kinase (ERK) pathway plays a major role in cellular responses and vascular diseases. In this study, we observed that the inhibition of ERK2 activity by recombinant adenovirus encoding antisense ERK2 (Adanti‐ERK2) significantly suppressed the proliferation, converting of cell cycle from G1 phase to S phase and directed migration, and partially abrogated transforming growth factor‐β1 (TGF‐β1) expression in VSMCs stimulated with PDGF‐BB. Ex vivo gene transfer of Adanti‐ERK2 into rat aortic allograft attenuated chronic transplant vasculopathy by the inhibition of VSMC proliferation and migration. In conclusion, ERK2 is involved in PDGF‐BB‐induced VSMCs proliferation, migration and TGF‐β1 expression and may be a potential therapeutic target for transplant vasculopathy.

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Increased mRNA Expression of Transforming Growth Factor Beta in the Arterial Wall of Chronically Rejected Renal Allografts in Humans

Cited by 7 publications

References 10 publications

AKT1 leader gene and downstream targets are involved in a rat model of kidney allograft tolerance

AKT1 leader gene and downstream targets are involved in a rat model of kidney allograft tolerance

Urine proteomes of healthy aging humans reveal extracellular matrix (ECM) alterations and immune system dysfunction

Antisense extracellular signal-regulated kinase-2 gene therapy inhibits platelet-derived growth factor-induced proliferation, migration and transforming growth factor-β₁expression in vascular smooth muscle cells and attenuates transplant vasculopathy

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Increased mRNA Expression of Transforming Growth Factor Beta in the Arterial Wall of Chronically Rejected Renal Allografts in Humans

Cited by 7 publications

References 10 publications

AKT1 leader gene and downstream targets are involved in a rat model of kidney allograft tolerance

AKT1 leader gene and downstream targets are involved in a rat model of kidney allograft tolerance

Urine proteomes of healthy aging humans reveal extracellular matrix (ECM) alterations and immune system dysfunction

Antisense extracellular signal-regulated kinase-2 gene therapy inhibits platelet-derived growth factor-induced proliferation, migration and transforming growth factor-β1expression in vascular smooth muscle cells and attenuates transplant vasculopathy

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Antisense extracellular signal-regulated kinase-2 gene therapy inhibits platelet-derived growth factor-induced proliferation, migration and transforming growth factor-β₁expression in vascular smooth muscle cells and attenuates transplant vasculopathy