A Temporal Map of Gene Expression Pattern During Zebrafish Liver Regeneration

Jagtap, Urmila; Sivadas, Ambily; Basu, S.; Verma, Ankit; Sivasubbu, Sridhar; Scaria, Vinod; Sachidanandan, Chetana

doi:10.1089/zeb.2019.1790

Cited by 5 publications

(7 citation statements)

References 47 publications

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“…However, the fluorescence continued to drop for another 24 hours after MTZ was removed from the water indicating the persistence of MTZ in the larvae that continued to cause liver damage. Similar observations have been made in adult fabp10a-nfsb liver [19] and in other tissue ablation models using nfsb-MTZ system [32]. By imaging and quantification of fluorescence we observed a robust recovery and regeneration of the liver to sizes comparable to undamaged state by 96 hours post damage i.e., 8 dpf (Fig.…”

Section: Bml-257 Shows Prophylactic and Regenerative Activity In Mtz Induced Liver Injury Model Of Zebrafishsupporting

confidence: 87%

“…Zebrafish has been used very successfully in studying liver development and diseases that affect the liver such as hereditary liver diseases [13], biliary defects [14,15], fatty liver diseases [16] and hepatocellular carcinoma [17,18]. We have previously characterized a cell-ablation model for liver damage and regeneration in the adult zebrafish [19]. Drug induced liver injury has been modeled in zebrafish with various drugs such as acetaminophen [20], ibuprofen [21], rifampicin and dexamethasone [22].…”

Section: Introductionmentioning

confidence: 99%

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BML-257, a small molecule that protects against drug induced liver injury in zebrafish

Jagtap

Basu

Lokhande

et al. 2022

Preprint

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The use of many essential drugs is restricted due to their deleterious effects on the liver. Molecules that can prevent or protect the liver from drug induced liver injury (DILI) would be valuable in such situations. We used hepatocyte-specific expression of bacterial nitroreductase in zebrafish to cause temporally controlled liver damage. This transgenic line was used to run a whole organism based chemical screen in zebrafish larvae. In this screen we identified BML-257, a potent small molecule AKT inhibitor, that protected the liver against metronidazole-induced liver injury. BML-257 also showed potent prophylactic and pro-regenerative activity in this liver damage model. BML-257 also showed remarkable protective action in two independent toxicological models of liver injury caused by acetaminophen and Isoniazid. This suggests that BML-257 may have the potential to protect against multiple kinds of drug induced liver injury.

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Section: Bml-257 Shows Prophylactic and Regenerative Activity In Mtz Induced Liver Injury Model Of Zebrafishsupporting

confidence: 87%

Section: Introductionmentioning

confidence: 99%

BML-257, a small molecule that protects against drug induced liver injury in zebrafish

Jagtap

Basu

Lokhande

et al. 2022

Preprint

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“…Damage to DNA was evaluated using an adaptation of the alkaline single-cell gel electrophoresis (comet) assay developed by Singh et al [ 40 ] and adapted by Raimundo et al [ 41 ] and Martins and Costa [ 42 ]. In brief, freshly-harvested gill samples were minced with pliers in 700 mL of cold PBS and centrifuged for 1 min at 1500 rpm.…”

Section: Methodsmentioning

confidence: 99%

“…Slides were neutralized in 0.2 M Tris-HCl (pH 7.5) and dried with methanol for archiving before analysis. Rehydrated slides were stained with GreenSafe (Nzytech, Lisbon, Portugal) [ 42 ] and analyzed with a DM 2500 LED microscope adapted for epifluorescence with an EL 6000-light source (Leica Microsystems). Scoring was done with CometScore 1.6 (TriTek, Sumerduck, VA, USA), with 100 nucleoids being analyzed per slide.…”

Section: Methodsmentioning

confidence: 99%

Localization and Bioreactivity of Cysteine-Rich Secretions in the Marine Gastropod Nucella lapillus

et al. 2021

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Marine biodiversity has been yielding promising novel bioproducts from venomous animals. Despite the auspices of conotoxins, which originated the paradigmatic painkiller Prialt, the biotechnological potential of gastropod venoms remains to be explored. Marine bioprospecting is expanding towards temperate species like the dogwhelk Nucella lapillus, which is suspected to secrete immobilizing agents through its salivary glands with a relaxing effect on the musculature of its preferential prey, Mytilus sp. This work focused on detecting, localizing, and testing the bioreactivity of cysteine-rich proteins and peptides, whose presence is a signature of animal venoms and poisons. The highest content of thiols was found in crude protein extracts from the digestive gland, which is associated with digestion, followed by the peribuccal mass, where the salivary glands are located. Conversely, the foot and siphon (which the gastropod uses for feeding) are not the main organs involved in toxin secretion. Ex vivo bioassays with Mytilus gill tissue disclosed the differential bioreactivity of crude protein extracts. Secretions from the digestive gland and peribuccal mass caused the most significant molecular damage, with evidence for the induction of apoptosis. These early findings indicate that salivary glands are a promising target for the extraction and characterization of bioactive cysteine-rich proteinaceous toxins from the species.

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“…To identify upstream regulators and canonical pathways involved in fin regeneration, we analyzed these RNA-seq data using ingenuity pathway analysis (IPA) (Krämer et al, 2014). The most highly activated upstream regulators were ERBB2, an EGF co-receptor implicated in zebrafish fin regeneration (Rojas-Muñoz et al, 2009), and MYC, a transcription factor central to cell growth and proliferation (Meyer and Penn, 2008) implicated in regeneration of liver, Müller glia and lateral line neuromasts in zebrafish (Jagtap et al, 2020;Lee et al, 2016;Mitra et al, 2019). The most downregulated upstream factor was TP53, a major cell cycle and apoptotic regulator that was described to be suppressed to facilitate salamander limb regeneration ( Fig.…”

Section: Introductionmentioning

confidence: 97%

Identification and requirements of enhancers that direct gene expression during zebrafish fin regeneration

Thompson

Lee

et al. 2020

Development

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To identify candidate tissue regeneration enhancer elements (TREEs) important for zebrafish fin regeneration, we performed ATAC-seq from bulk tissue or purified fibroblasts of uninjured and regenerating caudal fins. We identified tens of thousands of DNA regions from each sample type with dynamic accessibility during regeneration, and assigned these regions to proximal genes with corresponding expression changes by RNA-seq. To determine whether these profiles reveal bona fide TREEs, we tested the sufficiency and requirements of several sequences in stable transgenic lines and mutant lines with homozygous deletions. These experiments validated new non-coding regulatory sequences near induced and/or essential genes during fin regeneration, including fgf20a, mdka and cx43, identifying distinct domains of directed expression for each confirmed TREE. Whereas deletion of the previously identified LEN enhancer abolished detectable induction of the nearby leptin b gene during regeneration, deletions of enhancers linked to fgf20a, mdka and cx43 had no effect or partially reduced gene expression. Our study generates a new resource for dissecting the regulatory mechanisms of appendage generation and reveals a range of requirements for individual TREEs in control of regeneration programs.

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A Temporal Map of Gene Expression Pattern During Zebrafish Liver Regeneration

Cited by 5 publications

References 47 publications

BML-257, a small molecule that protects against drug induced liver injury in zebrafish

BML-257, a small molecule that protects against drug induced liver injury in zebrafish

Localization and Bioreactivity of Cysteine-Rich Secretions in the Marine Gastropod Nucella lapillus

Identification and requirements of enhancers that direct gene expression during zebrafish fin regeneration

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