Effect of retinoic acid-induced transglutaminase on cell growth in regenerating liver

Ohtake, Yosuke; Maruko, Akiko; Abe, Shinya; Fukumoto, Manabu; Ohkubo, Yasuhito

doi:10.2220/biomedres.27.75

Cited by 8 publications

(8 citation statements)

References 33 publications

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“…An in vitro study found that RA inhibited DNA synthesis in rat hepatocytes (Ikeda & Fujiwara, ). This result is consistent with an in vivo study, showing repression of proliferation upon RA treatment (Ohtake, Maruko, Abe, Fukumoto, & Ohkubo, ). However, RA was shown to have a mitogenic effect in other studies that utilized hepatocytes cultured upon liver resection (Ledda‐Columbano et al, ; You et al, ).…”

Section: Wound Signaling and The Regulation Of Proliferationsupporting

confidence: 92%

Wound‐induced cell proliferation during animal regeneration

Ricci

Srivastava

2018

WIREs Developmental Biology

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Many animal species are capable of replacing missing tissues that are lost upon injury or amputation through the process of regeneration. Although the extent of regeneration is variable across animals, that is, some animals can regenerate any missing cell type whereas some can only regenerate certain organs or tissues, regulated cell proliferation underlies the formation of new tissues in most systems. Notably, many species display an increase in proliferation within hours or days upon wounding. While different cell types proliferate in response to wounding in various animal taxa, comparative molecular data are beginning to point to shared wound-induced mechanisms that regulate cell division during regeneration. Here, we synthesize current insights about early molecular pathways of regeneration from diverse model and emerging systems by considering these species in their evolutionary contexts. Despite the great diversity of mechanisms underlying injury-induced cell proliferation across animals, and sometimes even in the same species, similar pathways for proliferation have been implicated in distantly related species (e.g., small diffusible molecules, signaling from apoptotic cells, growth factor signaling, mTOR and Hippo signaling, and Wnt and Bmp pathways). Studies that explicitly interrogate molecular and cellular regenerative mechanisms in understudied animal phyla will reveal the extent to which early pathways in the process of regeneration are conserved or independently evolved. This article is categorized under: Comparative Development and Evolution > Body Plan Evolution Adult Stem Cells, Tissue Renewal, and Regeneration > Regeneration Comparative Development and Evolution > Model Systems.

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Section: Wound Signaling and The Regulation Of Proliferationsupporting

confidence: 92%

Wound‐induced cell proliferation during animal regeneration

Ricci

Srivastava

2018

WIREs Developmental Biology

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“…Early in vitro studies reported that RA is a potent inhibitor of DNA synthesis in primary rat hepatocytes (9). Similarly, when administered after PH, RA disrupted rat hepatocyte proliferation in vivo by repressing early response genes and increasing the activity of transglutaminase and ornithinedecarboxylase (10–14). In contrast to these findings, other studies have shown that RA enhances hepatocyte proliferation and survival.…”

Section: Introductionmentioning

confidence: 99%

“…Another important factor to consider is the timing of exogenous RA administration. In the previous studies, RA was administered after surgical resection of the liver (10–14, 18). The hepatoprotective role of RA preconditioning has recently been proposed in an ischemic/reperfusion injury model (20), but there is no evidence in the literature that clearly documents the effects of RA treatment prior to PH-induced liver regeneration.…”

Section: Introductionmentioning

confidence: 99%

Retinoic acid regulates cell cycle genes and accelerates normal mouse liver regeneration

Liu

Ying

et al. 2014

Biochemical Pharmacology

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All-trans retinoic acid (RA) is a potent inducer of regeneration. Because the liver is the principal site for storage and bioactivation of vitamin A, the current study examines the effect of RA in mouse hepatocyte proliferation and liver regeneration. Mice that received a single dose of RA (25 μg/g) by oral gavage developed hepatomegaly with increased number of Ki67-positive cells and induced expression of cell cycle genes in the liver. DNA binding data revealed that RA receptors retinoic acid receptor β (RARβ) and retinoid x receptor α (RXRα) bound to cell cycle genes Cdk1, Cdk2, Cyclin B, Cyclin E, and Cdc25a in mice with and without RA treatment. In addition, RA treatment induced novel binding of RARβ/RXRα to Cdk1, Cdk2, Cyclin D, and Cdk6 genes. All RARβ/RXRα binding sites contained AGGTCA-like motifs. RA treatment also promoted liver regeneration after partial hepatectomy (PH). RA signaling was implicated in normal liver regeneration as the mRNA levels of RARβ, Aldh1a2, Crabp1, and Crbp1 were all induced 1.5 days after PH during the active phase of hepatocyte proliferation. RA treatment prior to PH resulted in early up-regulation of RARβ, Aldh1a2, Crabp1, and Crbp1, which was accompanied by an early induction of cell cycle genes. Western blotting for RARβ, c-myc, Cyclin D, E, and A further supported the early induction of retinoid signal and cell proliferation by RA treatment. Taken together, our data suggest that RA may regulate cell cycle progression and accelerates liver regeneration. Such effect is associated with an early induction of RA signaling, which includes increased expression of the receptor, binding proteins, and processing enzyme for retinoids.

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“…A study in rats [25] and other studies have confirmed the role of retinoic acid in the expression of TG-1 [26] and TG-2 [27]. Because TG-1 has a role in ocular surface keratinization, some studies have focused on other upstream triggers of TG-1 including interferon gamma (IFN-γ) [28].…”

Section: Discussionmentioning

confidence: 99%

Transglutaminases (TGs) in Ocular and Periocular Tissues: Effect of Muscarinic Agents on TGs in Scleral Fibroblasts

et al. 2011

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ObjectiveTo investigate the expression of transglutaminases (TGs) in the ocular surface, the eyelid margin and associated glands and to determine effect of muscarinic agents on TGs in scleral fibroblasts (SF).Materials and MethodsPrimary SFs cultured from mouse and human sclera were treated with atropine and carbachol for 5 days. Lysed cell RNA was used for real-time PCR, protein was used for Western blot analysis and TG-2 transamidase activity was measured by ELISA. Immunohistochemistry was done to determine the expression of TGases.ResultsImmunohistochemistry and western blot confirmed the expression of TGs-1, 2, 3 and 5 proteins in cultured SFs and eye tissues. Real time PCR showed TG-1, 2, 5 transcript levels to be down regulated 3 fold (p<0.05) in cultured human and mouse SFs after incubation with atropine and this was reversed by carbachol. However, TG-3 expression was increased with atropine and decreased with carbachol at all concentrations. Atropine abrogated the carbachol-induced activation of SF in a dose-dependent manner. TGs-1, 3, 5 were localized in the entire mouse corneal epithelium, stroma and endothelium but TG-2 was present only in the corneal subepithelium and stroma. All TGs were localized in mouse Meibomian glands however TG-2 had a weak expression.ConclusionsOur results confirm that TGs-1, 2, 3 and 5 are expressed in human SF and murine ocular tissues, eyelid and associated Meibomian glands. Real-time PCR and Western blot results showed that muscarinic antagonist down-regulates TGs-1, 2 and 5 in both cultured human and mouse SFs and upregulates TG-3. Atropine abrogated the carbachol-induced activation of SF in a dose-dependent manner. These results suggest that manipulation of TGs by way of muscarinic receptor acting drugs may be a plausible method of intervention in wound healing and scleral remodeling.

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Effect of retinoic acid-induced transglutaminase on cell growth in regenerating liver

Cited by 8 publications

References 33 publications

Wound‐induced cell proliferation during animal regeneration

Wound‐induced cell proliferation during animal regeneration

Retinoic acid regulates cell cycle genes and accelerates normal mouse liver regeneration

Transglutaminases (TGs) in Ocular and Periocular Tissues: Effect of Muscarinic Agents on TGs in Scleral Fibroblasts

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