Heme oxygenase and renal disease

Jarmi, Tambi; Agarwal, Anupam

doi:10.1007/s11906-009-0011-z

Cited by 85 publications

(62 citation statements)

References 60 publications

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“…It is known that HO-1 has an important protective role in many aspects of normal physiology and pathological states [58,60]. Moreover, HO-1 deficiency is associated with increased fibrosis, tubular TGFb1 expression, inflammation, and enhanced EMT in obstructive kidney disease [61,62]. Thus, higher HO-1 expression in the kidneys of MSC-treated animals may abrogate fibrosis progression.…”

Section: Discussionmentioning

confidence: 99%

Mesenchymal Stem Cells Attenuate Renal Fibrosis Through Immune Modulation and Remodeling Properties in a Rat Remnant Kidney Model

et al. 2009

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Mesenchymal stem cells (MSCs) have regenerative properties in acute kidney injury, but their role in chronic kidney diseases is still unknown. More specifically, it is not known whether MSCs halt fibrosis. The purpose of this work was to investigate the role of MSCs in fibrogenesis using a model of chronic renal failure. MSCs were obtained from the tibias and femurs of male Wistar-EPM rats. Female Wistar rats were subjected to the remnant model, and 2|3|10 5 MSCs were intravenously administrated to each rat every other week for 8 weeks or only once and followed for 12 weeks. SRY gene expression was observed in female rats treated with male MSCs, and immune localization of CD73 1 CD90 1 cells at 8 weeks was also assessed. Serum and urine analyses showed an amelioration of functional parameters in MSC-treated animals at 8 weeks, but not at 12 weeks. Masson's trichrome and Sirius red staining demonstrated reduced levels of fibrosis in MSC-treated animals. These results were corroborated by reduced vimentin, type I collagen, transforming growth factor b, fibroblast specific protein 1 (FSP-1), monocyte chemoattractant protein 1, and Smad3 mRNA expression and a smooth muscle actin and FSP-1 protein expression. Renal interleukin (IL)-6 and tumor necrosis factor a mRNA expression levels were significantly decreased after MSC treatment, whereas IL-4 and IL-10 expression levels were increased. All serum cytokine expression levels were decreased in MSC-treated animals. Taken together, these results suggested that MSC therapy can indeed modulate the inflammatory response that follows the initial phase of a chronic renal injury. The immunosuppressive and remodeling properties of MSCs may be involved in the decreased fibrosis in the kidney.

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Section: Discussionmentioning

confidence: 99%

Mesenchymal Stem Cells Attenuate Renal Fibrosis Through Immune Modulation and Remodeling Properties in a Rat Remnant Kidney Model

et al. 2009

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“…We suggest that the Rev-erba/PGC-1a cycle regulates intracellular heme concentration within the physiological range. This negative feedback mechanism would function to help prevent heme concentrations from reaching pathological levels that require detoxification by the HMOX1 system (Furuyama et al 2007;Jarmi and Agarwal 2009). In addition, and uniquely, the relief of this negative feedback provides a transcriptional sensing mechanism to stimulate heme biosynthesis when its levels are low.…”

Section: Discussionmentioning

confidence: 99%

Negative feedback maintenance of heme homeostasis by its receptor, Rev-erbα

Wu¹,

Yin²,

Hanniman³

et al. 2009

Genes Dev.

107

101

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Intracellular heme levels must be tightly regulated to maintain proper mitochondrial respiration while minimizing toxicity, but the homeostatic mechanisms are not well understood. Here we report a novel negative feedback mechanism whereby the nuclear heme receptor Rev-erba tightly controls the level of its own ligand. Heme binding to Rev-erba recruits the NCoR/histone deacetylase 3 (HDAC3) corepressor complex to repress the transcription of the coactivator PGC-1a, a potent inducer of heme synthesis. Depletion of Rev-erba derepresses PGC-1a, resulting in increased heme levels. Conversely, increased Rev-erba reduces intracellular heme, and impairs mitochondrial respiration in a heme-dependent manner. Consistent with this bioenergetic impairment, overexpression of Rev-erba dramatically inhibits cell growth due to a cell cycle arrest. Thus, Rev-erba modulates the synthesis of its own ligand in a negative feedback pathway that maintains heme levels and regulates cellular energy metabolism.[Keywords: Rev-erba; PGC-1a; heme homeostasis; mitochondria; energy] Supplemental material is available at http://www.genesdev.org.

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“…HO-1, an acute stress marker, is known to be a microsomal enzyme that catalyzes the oxidation of heme to the antioxidant molecules, biliverdin and carbon monoxide. 29 The expression of HO-1 is induced by oxidative stress. GPX-1, a member of the glutathione peroxidase family, plays an important role for the detoxification of hydrogen peroxide, and is one of the most important antioxidant enzymes.…”

Section: Discussionmentioning

confidence: 99%

Urinary Excretion of Liver Type Fatty Acid Binding Protein Accurately Reflects the Degree of Tubulointerstitial Damage

Yokoyama

Kamijo‐Ikemori

Sugaya

et al. 2009

The American Journal of Pathology

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To investigate the relationship between liver-type fatty acid-binding protein (L-FABP), a biomarker of chronic kidney disease, in the kidney and the degree of tubulointerstitial damage, folic acid (FA)-induced nephropathy was studied in a mouse model system. As renal L-FABP is not expressed in wild-type mice, human L-FABP (hL-FABP) transgenic mice were used in this study. hL-FABP is expressed in the renal proximal tubules of the transgenic mice that were injected intraperitoneally with FA in NaHCO 3 (the FA group) or only NaHCO 3 (the control group) and oral saline solution daily during the experimental period. The FA group developed severe tubulointerstitial damage with the infiltration of macrophages and the deposition of type I collagen on days 3 and 7 and recovered to the control level on day 14. The gene and protein expression levels of hL-FABP in the kidney were significantly enhanced on days 3 and 7. Urinary hL-FABP in the FA group was elevated on days 3 and 7 and decreased to the control level on day 14. The protein expression levels of hL-FABP in both the kidney and urine significantly correlated with the degree of tubulointerstitial damage, the infiltration of macrophages, and the deposition of type I collagen. In conclusion, renal expression and urinary excretion of hL-FABP significantly reflected the severity of tubulointerstitial damage in FA-induced nephropathy.

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Heme oxygenase and renal disease

Cited by 85 publications

References 60 publications

Mesenchymal Stem Cells Attenuate Renal Fibrosis Through Immune Modulation and Remodeling Properties in a Rat Remnant Kidney Model

Mesenchymal Stem Cells Attenuate Renal Fibrosis Through Immune Modulation and Remodeling Properties in a Rat Remnant Kidney Model

Negative feedback maintenance of heme homeostasis by its receptor, Rev-erbα

Urinary Excretion of Liver Type Fatty Acid Binding Protein Accurately Reflects the Degree of Tubulointerstitial Damage

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