Heme Oxygenase-1 Deficiency Promotes Epithelial-Mesenchymal Transition and Renal Fibrosis

Kie, Jeong Hae; Kapturczak, Matthias H.; Traylor, Amie M.; Agarwal, Anupam; Hill‐Kapturczak, Nathalie

doi:10.1681/asn.2007101099

Cited by 87 publications

(75 citation statements)

References 58 publications

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“…47,48 Kidney cortices from mice were dissected from the medulla, sliced, minced, and filtered through a 70-m cell strainer over a 50-ml conical tube with media (Renal Epithelial Cell Growth Medium; PromoCell). The medium containing the tubules was centrifuged and plated on collagencoated culture plates and then incubated for 72 hours at 37°C in 5% CO 2 .…”

Section: Generation Of Proximal Tubule Epithelial Cells From Micementioning

confidence: 99%

“…Cells were examined for expression of ␥-glutamyltranspeptidase and alkaline phosphatase, markers for proximal tubule cells, as described previously. 47 Cisplatin Injury Model …”

Section: Generation Of Proximal Tubule Epithelial Cells From Micementioning

confidence: 99%

“…47 Briefly, cell cultures were lysed in RIPA buffer, electrophoresed in a 15% SDS-polyacrylamide gel, and transferred onto a Hybond C Extra membrane (Amersham Biosciences). Membranes were incubated with anti-HO-1 (1:5000 dilution; Stressgen), anti-LC3 (1:2000 dilution, Sigma-Aldrich), anti-cleaved caspase-3 (1:2000 dilution; Cell Signaling), anti-beclin (1:2000 dilution; Santa Cruz Biotechnology), or anti-Atg5 (1:5000 dilution; Millipore) antibodies, followed by a peroxidase-conjugated goat anti-rabbit (or mouse) IgG antibody (1: 10000 dilution; Jackson ImmunoResearch Laboratories, West Grove, PA).…”

Section: Western Blot Analysismentioning

confidence: 99%

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Heme Oxygenase-1 Inhibits Renal Tubular Macroautophagy in Acute Kidney Injury

Bolisetty

Traylor²,

Kim³

et al. 2010

Journal of the American Society of Nephrology

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143

125

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Autophagy is a tightly regulated, programmed mechanism to eliminate damaged organelles and proteins from a cell to maintain homeostasis. Cisplatin, a chemotherapeutic agent, accumulates in the proximal tubules of the kidney and causes dose-dependent nephrotoxicity, which may involve autophagy. In the kidney, cisplatin induces the protective antioxidant heme oxygenase-1 (HO-1). In this study, we examined the relationship between autophagy and HO-1 during cisplatin-mediated acute kidney injury (AKI). In wild-type primary proximal tubule cells (PTC), we observed a time-dependent increase in autophagy after cisplatin. In HO-1 Ϫ/Ϫ PTC, however, we observed significantly higher levels of basal autophagy, impaired progression of autophagy, and increased apoptosis after cisplatin. Restoring HO-1 expression in these cells reversed the autophagic response and inhibited apoptosis after treatment with cisplatin. In vivo, although both wild-type and HO-1-deficient mice exhibited autophagosomes in the proximal tubules of the kidney in response to cisplatin, HO-1-deficient mice had significantly more autophagosomes, even in saline-treated animals. In addition, ecdysone-induced overexpression of HO-1 in cells led to a delay in autophagy progression, generated significantly lower levels of reactive oxygen species, and protected against cisplatin cytotoxicity. These findings demonstrsate that HO-1 inhibits autophagy, suggesting that the heme oxygenase system may contain therapeutic targets for AKI.

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Section: Generation Of Proximal Tubule Epithelial Cells From Micementioning

confidence: 99%

“…Cells were examined for expression of ␥-glutamyltranspeptidase and alkaline phosphatase, markers for proximal tubule cells, as described previously. 47 Cisplatin Injury Model …”

Section: Generation Of Proximal Tubule Epithelial Cells From Micementioning

confidence: 99%

Section: Western Blot Analysismentioning

confidence: 99%

See 1 more Smart Citation

Heme Oxygenase-1 Inhibits Renal Tubular Macroautophagy in Acute Kidney Injury

Bolisetty

Traylor²,

Kim³

et al. 2010

Journal of the American Society of Nephrology

Self Cite

143

125

View full text Add to dashboard Cite

show abstract

“…The protective effect of HO-1 against kidney injury is well known in a variety of animal models. 2,18,[22][23][24][25][26] We therefore performed an association study in patients with CAD to investigate whether the length polymorphism of the HO-1 gene promoter is associated with the risk of CKD.…”

mentioning

confidence: 99%

Length Polymorphism in Heme Oxygenase-1 and Risk of CKD among Patients with Coronary Artery Disease

Chen

Kuo

Hung

et al. 2014

Journal of the American Society of Nephrology

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The length polymorphism of guanosine thymidine dinucleotide repeats in the heme oxygenase-1 gene promoter is associated with cardiovascular events and mortality in high-risk populations. Experimental data suggest that heme oxygenase-1 protects against kidney disease. However, the association between this polymorphism and long-term risk of CKD in high-risk patients is unknown. We analyzed the allelic frequencies of guanosine thymidine dinucleotide repeats in the heme oxygenase-1 gene promoter in 386 patients with coronary artery disease recruited from January 1999 to July 2001 and followed until August 31, 2012. The S allele represents short repeats (,27), and the L allele represents long repeats ($27). The primary renal end points consisted of sustained serum creatinine doubling and/or ESRD requiring long-term RRT. The secondary end points were major adverse cardiovascular events and mortality. At the end of study, the adjusted hazard ratios (95% confidence intervals) for each L allele in the additive model were 1.99 (1.27 to 3.14; P=0.003) for the renal end points, 1.70 (1.27 to 2.27; P,0.001) for major adverse cardiovascular events, and 1.36 (1.04 to 1.79; P=0.03) for mortality. With cardiac events as time-dependent covariates, the adjusted hazard ratio for each L allele in the additive model was 1.91 (1.20 to 3.06; P=0.01) for the renal end points. In conclusion, a greater number of guanosine thymidine dinucleotide repeats in the heme oxygenase-1 gene promoter is associated with higher risk for CKD, cardiovascular events, and mortality among patients with coronary artery disease.

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“…5 Subsequently, induction of HO-1 was recognized as a protective response that can occur in all organs and tissues and against virtually any insult. 3,4,[6][7][8][9][10] At least four features of HO-1 underlie its salutary effects in stressed tissues. 11,12 First, HO activity generates three chemically distinct products-carbon monoxide, bile pigments, and iron-each of which can participate in specific cellular processes; induced HO-1 thus transmits broad-based and far-ranging signals through its tripartite products and their respective downstream effects.…”

mentioning

confidence: 99%

Human AKI and Heme Oxygenase-1

Nath

2012

Journal of the American Society of Nephrology

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Heme Oxygenase-1 Deficiency Promotes Epithelial-Mesenchymal Transition and Renal Fibrosis

Cited by 87 publications

References 58 publications

Heme Oxygenase-1 Inhibits Renal Tubular Macroautophagy in Acute Kidney Injury

Heme Oxygenase-1 Inhibits Renal Tubular Macroautophagy in Acute Kidney Injury

Length Polymorphism in Heme Oxygenase-1 and Risk of CKD among Patients with Coronary Artery Disease

Human AKI and Heme Oxygenase-1

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