Progressive histone alterations and proinflammatory gene activation: consequences of heme protein/iron-mediated proximal tubule injury

Zager, Richard A.; Johnson, Ali C. M.

doi:10.1152/ajprenal.00683.2009

Cited by 32 publications

(28 citation statements)

References 49 publications

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“…Nath et al [16] described that repetitive episodes of rhabdomyolysis induced an attenuated renal response to weekly glycerol IM injections after one month, also resulting in a mild decrease in CrCl (≈-15%) and absent structural kidney changes were reported at this time point. Nevertheless, rhabdomyolysis induced a persistent and increasingly pro-inflammatory state in the kidney, despite the apparent AKI resolution [20]. In the present study, we combined both insults to resemble heat stress nephropathy and found a 45% fall in CrCl, a further increase in NAG urine excretion (in comparison to W + V group reported in ref.…”

Section: Discussionsupporting

confidence: 55%

Kidney Injury from Recurrent Heat Stress and Rhabdomyolysis: Protective Role of Allopurinol and Sodium Bicarbonate

et al. 2018

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Background: Heat stress and rhabdomyolysis are major risk factors for the occurrence of repeated acute kidney injury in workers exposed to heat and strenuous work. These episodes, in turn, may progress to chronic kidney disease. Objective: The purpose of this study was to test the effect of allopurinol (AP) and sodium bicarbonate on the kidney injury induced by recurrent heat stress dehydration with concomitant repeated episodes of rhabdomyolysis. Methods: The model consisted of heat stress exposure (1 h, 37°C) plus rhabdomyolysis (R) induced by repetitive IM injections of glycerol (7.5 mL/kg BW days) in the rat. In addition, to replicate the human situation, uricase was inhibited (oxonic acid [OA] 750 mg/K/d) to increase uric acid (UA) levels. Additional groups were treated either with AP 150 mg/L, n = 10, bicarbonate (BC; 160 mM, n = 10), or both (AP + BC, n = 10) in drinking water. We also included 2 control groups consisting of normal controls (N-Ref, n = 5) and uricase-inhibited rats (OA, n = 5) that were not exposed to heat or muscle injury. Groups were studied for 35 days. Results: Uricase-inhibited rats exposed to heat and rhabdomyolysis developed pathway and increased intrarenal oxidative stress and inflammasome activation. Kidney injury could be largely prevented by AP, and also BC, although the treatments were not synergistic. Conclusion: Increased levels of UA may play an important role in the renal alterations induced by heat stress and continuous episodes of rhabdomyolysis. Therefore, treatments aimed to reduce hyperuricemia may help to decrease the renal burden in these conditions. Clinical trials are suggested to test whether this is also true in humans.

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Section: Discussionsupporting

confidence: 55%

Kidney Injury from Recurrent Heat Stress and Rhabdomyolysis: Protective Role of Allopurinol and Sodium Bicarbonate

et al. 2018

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“…Evidence shows that TGF-␤1 can regulate epigenetic modifications to regulate target genes in diverse cell types, including vascular smooth muscle cells (42), ovarian (63), and mammary epithelial cells (61), immune cells (66), and fibroblasts (15). Reports show that histone modifications including H3K9Ac and H3K4 methylation (H3K4me) play a role in PMA-induced laminin gene expression in rat mesangial cells (35) and in inflammatory gene expression in tubular cells from acute renal injury models (34,65). Our recent studies demonstrated that TGF-␤1 can induce significant changes in promoter histone H3K4me and H3K9me at the promoters of differentially regulated profibrotic genes CTGF, Col1a1, and PAI-1 in MCs (51).…”

Section: F607 Histone Acetylation In Tgf-␤1-mediated Actionsmentioning

confidence: 99%

Involvement of p300/CBP and epigenetic histone acetylation in TGF-β1-mediated gene transcription in mesangial cells

Yuan

Reddy

Sun

et al. 2013

American Journal of Physiology-Renal Physiology

130

119

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Transforming growth factor-β1 (TGF-β1)-induced expression of plasminogen activator inhibitor-1 (PAI-1) and p21 in renal mesangial cells (MCs) plays a major role in glomerulosclerosis and hypertrophy, key events in the pathogenesis of diabetic nephropathy. However, the involvement of histone acetyl transferases (HATs) and histone deacetylases (HDACs) that regulate epigenetic histone lysine acetylation, and their interaction with TGF-β1-responsive transcription factors, are not clear. We evaluated the roles of histone acetylation, specific HATs, and HDACs in TGF-β1-induced gene expression in rat mesangial cells (RMCs) and in glomeruli from diabetic mice. Overexpression of HATs CREB binding protein (CBP) or p300, but not p300/CBP-activating factor, significantly enhanced TGF-β1-induced PAI-1 and p21 mRNA levels as well as transactivation of their promoters in RMCs. Conversely, they were significantly attenuated by HAT domain mutants of CBP and p300 or overexpression of HDAC-1 and HDAC-5. Chromatin immunoprecipitation assays showed that TGF-β1 treatment led to a time-dependent enrichment of histone H3-lysine9/14-acetylation (H3K9/14Ac) and p300/CBP occupancies around Smad and Sp1 binding sites at the PAI-1 and p21 promoters. TGF-β1 also enhanced the interaction of p300 with Smad2/3 and Sp1 and increased Smad2/3 acetylation. High glucose-treated RMCs exhibited increased PAI-1 and p21 levels, and promoter H3K9/14Ac, which were blocked by TGF-β1 antibodies. Furthermore, increased PAI-1 and p21 expression was associated with elevated promoter H3K9/14Ac levels in glomeruli from diabetic mice. Thus TGF-β1-induced PAI-1 and p21 expression involves interaction of p300/CBP with Smads and Sp1, and increased promoter access via p300/CBP-induced H3K9/14Ac. This in turn can augment glomerular dysfunction linked to diabetic nephropathy.

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“…Complex interactions between heme oxygenase and TGF-β1, over time, in specific cell subsets, may have ameliorative or maladaptive consequences. 15,58,59 The lack of renal tissue from patients with AKI and suitable controls has been identified as a barrier to enhancing our understanding of factors associated with outcomes in patients with AKI. 2,60 The National Institute of Diabetes, Digestive and Kidney Diseases (NIDDK) supports the Assessment, Serial Evaluation and Subsequent Sequelae of AKI (ASSESS AKI) study, which prospectively evaluates long-term outcomes of hospitalized patients, with and without CKD, after an episode of AKI, to determine the natural history of AKI and delineate risk factors for progression and development of complications, including CVD.…”

Section: Mechanisms Associated With Progressive Renal Injurymentioning

confidence: 99%

Acute Kidney Injury and Chronic Kidney Disease

Chawla

Kimmel

2015

Chronic Renal Disease

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Progressive histone alterations and proinflammatory gene activation: consequences of heme protein/iron-mediated proximal tubule injury

Abstract: Zager RA, Johnson AC. Progressive histone alterations and proinflammatory gene activation: consequences of heme protein/iron-mediated proximal tubule injury.

Cited by 32 publications

References 49 publications

Kidney Injury from Recurrent Heat Stress and Rhabdomyolysis: Protective Role of Allopurinol and Sodium Bicarbonate

Kidney Injury from Recurrent Heat Stress and Rhabdomyolysis: Protective Role of Allopurinol and Sodium Bicarbonate

Involvement of p300/CBP and epigenetic histone acetylation in TGF-β1-mediated gene transcription in mesangial cells

Acute Kidney Injury and Chronic Kidney Disease

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