Leukemia Inhibitory Factor Is Involved in Tubular Regeneration after Experimental Acute Renal Failure

Yoshino, Mihoko; Monkawa, Toshiaki; Tsuji, Mihoko; Hayashi, Matsuhiko; Saruta, Takao

doi:10.1097/01.asn.0000101180.96787.02

Cited by 58 publications

(46 citation statements)

References 45 publications

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“…We next examined the changes in the histone acetylation in the recovery phase after transient energy depletion. Consistent with the results published previously, 19 the ATP contents were stored to the levels not significantly different from those measured just before the incubation with antimycin A (98.5 Ϯ 3.0% of the value obtained just before incubation with antimycin A; n ϭ 5; P Ͼ 0.05) at 4 h after washout of antimycin A. In parallel with the recovery of the ATP levels, the histone acetylation levels also recovered to baseline levels by 4 h after the washout of antimycin A ( Figure 3A).…”

Section: Histone Remodeling After Transient Energy Depletion In Kidnesupporting

confidence: 83%

“…On the basis of the finding that the activity of HDAC5 regulates the histone acetylation level, we next investigated the possibility that HDAC5 downregulation may induce alterations in the expressions of LIF and BMP7, which are known to be induced in the renal tubules in the recovery phase after ischemia. 19,20 Consistent with previous reports, 19,20 the mRNA levels of LIF and BMP7 both were increased after transient energy depletion ( Figure 5C). Moreover, the mRNA level of BMP7 was significantly increased in the cells treated with HDAC5 Stealth RNAi as compared with that in the cells treated with control RNAi, whereas that of LIF was unchanged ( Figure 5D).…”

Section: Downregulation Of Hdac5 After Transient Energy Depletion Indsupporting

confidence: 81%

“…17,18 Proteins such as leukemia inhibitory factor (LIF) and bone morphogenetic protein-7 (BMP7), which play pivotal roles in nephron formation during kidney development, have been shown to be induced and to contribute critically to the proliferation and repair of the tubular cells after ischemia. 11,19,20 In addition, administration of BMP7 has been shown to exert beneficial effects in various models of renal injury. [21][22][23] The elucidation of mechanisms underlying the induction of protective factors after ischemic insult is of great potential importance from the viewpoint of development of therapy aimed at organ repair after injury.…”

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confidence: 99%

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Epigenetic Regulation of BMP7 in the Regenerative Response to Ischemia

Marumo

Hishikawa

Yoshikawa

et al. 2008

Journal of the American Society of Nephrology

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Kidneys damaged by ischemia have the potential to regenerate through a mechanism involving intrarenal induction of protective factors, including bone morphogenetic protein-7 (BMP7). Epigenetic changes, such as alterations in histone modifications, have also been shown to play a role in various pathologic conditions, but their involvement in ischemic injury and regeneration remains unknown. This study investigated whether changes in histone acetylation, regulated by histone acetyltransferase and histone deacetylase (HDAC), are induced by renal ischemia and involved in the regenerative response. Ischemia/reperfusion of the mouse kidney induced a transient decrease in histone acetylation in proximal tubular cells, likely as a result of a decrease in histone acetyltransferase activity as suggested by experiments with energy-depleted renal epithelial cells in culture. During recovery after transient energy depletion in epithelial cells, the HDAC isozyme HDAC5 was selectively downregulated in parallel with the return of acetylated histone. Knockdown of HDAC5 by RNAi significantly increased histone acetylation and BMP7 expression. BMP7 induction and HDAC5 downregulation in the recovery phase were also observed in proximal tubular cells in vivo after transient ischemia. These data indicate that ischemia induces dynamic epigenetic changes involving HDAC5 downregulation, which contributes to histone re-acetylation and BMP7 induction in the recovery phase. This highlights HDAC5 as a modulator of the regenerative response after ischemia and suggests HDAC5 inhibition may be a therapeutic strategy to enhance BMP7 expression.

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Section: Histone Remodeling After Transient Energy Depletion In Kidnesupporting

confidence: 83%

Section: Downregulation Of Hdac5 After Transient Energy Depletion Indsupporting

confidence: 81%

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confidence: 99%

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Epigenetic Regulation of BMP7 in the Regenerative Response to Ischemia

Marumo

Hishikawa

Yoshikawa

et al. 2008

Journal of the American Society of Nephrology

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“…The two cell types seem to share a common expression profile for the LIFR gene. The LIFR protein participates in embryo implantation, in the differentiation of neural stem cells to astrocytes (80), as well as in the mesenchyme to epithelial conversion (81). Its role has been reported to be connected to the PTEN-Akt-FOXO axis and STAT3 (80).…”

Section: Cytokine/cytokine Interactionsmentioning

confidence: 99%

Pathway simulations in common oncogenic drivers of leukemic and rhabdomyosarcoma cells: A systems biology approach

et al. 2012

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Abstract. A part of current research has intensively been focused on the proliferation and metabolic processes governing biological systems. Since the advent of high throughput methodologies such as microarrays, the load of genomic data has increased geometrically and along with that the need for computational methods to interpret these data. In the present study, we investigated in vitro the common proliferation and metabolic processes, associated with common oncogenic pathways, as far as gene expression is concerned, between the T-cell acute lymphoblastic leukemia (CCRF-CEM) and the rhabdomyosarcoma (TE-671) cell lines. We present a computational approach, using cDNA microarrays, in order to identify commonalities between diverse biological systems. Our analysis predicted that JAK1, STAT1, PIAS2 and CDK4 are the driving forces in the two cell lines. This type of analysis may lead to the understanding of the common mechanisms that transform physiological cells to malignant, and may reveal a new holistic approach to understanding the dynamics of tumor onset as well as the mechanistics behind oncogenic drivers. IntroductionIt is a fact that tumors can be as diverse as the patients carrying them. Due to these differences, tumors are extremely difficult to cure, as the effects of treatments differ depending on the patient. Previously, Nicolis showed that stem cells are found in different tumor types, suggesting that they can be the etiology of tumor maintenance and growth (1). However, there is evidence that even normal, already differentiated cells can be transformed into tumorigenic ones (1). Perilongo et al also reported a case of a child manifesting five different tumor types simultaneously (2). It may be possible that stem cells originating from the same organism possess similar mutations or alterations, thus giving rise to five different tumor types. Therefore, there is a need for the investigation of common pathways between different tumor types. The discovery of similar or opposite gene expression profiles could lead us to the understanding of a common tumor origin, if such exists.A number of studies have investigated the detection of cancer germ line genes (CGGs) both in pediatric sarcomas (3) and pediatric brain tumors (4). The discovery of global antigens for tumor vaccines could become salvatory for childhood malignancies (3). Other studies have reported the common appearance of antigens in Ewing's sarcoma/primitive neuroectodermal tumor (EWS/PNET) with lymphoblastic lymphoma (5). Rhabdomyosarcoma (RMS) belongs to the PNET family of tumors, which utilize embryonic genes for their progression (6). Acute lymphoblastic leukemia (ALL), which originates from the lymphoblast, also uses embryonic mechanisms for its differentiation and progression.Another point which requires attention is the regulation of genes through transcription factors (TFs). Knowledge of gene regulatory networks is considered to be of crucial importance for understanding diseases such as cancer, and may lead to new therapeutic approaches...

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“…Tissue regeneration is thought to recapitulate developmental paradigms in various organs. Several developmental genes indispensable for kidney organogenesis, such as Pax-2 (10, 15), Wnt4 (30), and LIF (37), have been demonstrated to be reactivated in regenerating tubules after injury, thus suggesting the similarity of kidney development and repair.…”

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confidence: 99%