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Immunogold localization of hypoxia-inducible factor (HIF-1α) using polyclonal antibodies in the respiratory intestine of the bronze corydoras (Corydoras aeneus). Note numerous gold particles (arrowheads) for HIF-1α epitopes in the fibroblasts (a–c). No signal is visible in the case of the negative control, where the incubation with primary antibodies was omitted (d). Abbreviations: Fb, fibroblast; N, nucleus. Scale bar, 200 nm
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Bronze corydoras (Corydoras aeneus) is a small diurnal activity fish from South America. Under hypoxia conditions, it uses the posterior part of the intestine as an accessory respiratory organ. The present PCR studies demonstrated higher expression of HIF-1α (hypoxia-inducible factor) gene in the respiratory than that in digestive part of bronze co...
Citations
... 2b, 3)-were found to play an important role in stimulating the development of organs for air breathing in the early terrestrial vertebrates (Jonz 2018;Smatresk 1990). Thus, the most important factors associated with proliferation of AT1 cells, such as HIF-1α, NECs and EGFR, are present in the GBF (Satora and Winnicki 2000;Satora et al. 2017;Mytych et al. 2018;Satora et al. 2018). GBF antibodies directed against human EGFR and HIF-1α were successfully used in immunohistochemical and western blot studies Satora et al. 2018), which additionally facilitates the observations. ...
... Thus, the most important factors associated with proliferation of AT1 cells, such as HIF-1α, NECs and EGFR, are present in the GBF (Satora and Winnicki 2000;Satora et al. 2017;Mytych et al. 2018;Satora et al. 2018). GBF antibodies directed against human EGFR and HIF-1α were successfully used in immunohistochemical and western blot studies Satora et al. 2018), which additionally facilitates the observations. The research on signals and interactions between those elements in conditions of hypoxia makes it possible to observe a "switching pulse" initiating the proliferation of squamous epithelial cells (Fig. 3). ...
There is much evidence that the vertebrate lung originated from a progenitor structure which was present in bony fish. However, critical basic elements for the evolution of breathing in tetrapods, such as the central rhythm generator sensitive to CO2/pH and the pulmonary surfactant, were present in the lungless primitive vertebrate. This suggests that the evolution of air breathing in all vertebrates may have evolved through exaptations. It appears that the capability for proliferation of alveolar type 1 (AT1) cells is the “critical factor” which rendered possible the most radical subsequent innovation—the possibility of air breathing. “Epithelial remodeling,” which consists in proliferation of alveolar cells—the structural basis for gas diffusion—observed in the alimentary tract of the gut-breathing fishes (GBF) has great potential for application in biomedical research. Such a process probably led to the gradual evolutionary development of lungs in terrestrial vertebrates. Research on the cellular and molecular mechanisms controlling proliferation of squamous epithelial cells in the GBF should contribute to explaining the regeneration-associated phenomena that occur in mammal lungs, and especially to the understanding of signal pathways which govern the process.
... When the DO in water exceeds 5 mg/L, fish can carry out normal life activities; however, when the DO content is reduced to 2-3 mg/L, fish will appear floating on their head. When DO is < 1 mg/L, most fish will die due to a lack of oxygen (Satora et al. 2018). Hypoxia has occurred in cobia fish culture areas in recent years, due to a number of factors (Diaz 2001;Vaquer-Sunyer and Duarte 2008;Lai et al. 2016), such as water temperature, season, and culture density. ...
... It then affects proteins and cytokines, which alter behavior, growth and development, physiology, biochemistry, and metabolism, resulting in a decrease in growth, reproduction, and immunity. Finally, hypoxia affects the energy flow and ecological characteristics of the population (Satora et al. 2018;Chang et al. 2018;Jenne and Kubes 2013). Hence, the molecular mechanisms of cobia fish in response to hypoxia should be investigated. ...
... In mammals, as a transcriptional regulator, hif-1 comprises two subunits, hif-1a and hif-1b, which regulate the expression of genes related to growth, development, amino acid metabolism, and protein synthesis (Satora et al. 2018). hif-1α is the core regulator of the hypoxia response, which is also crucial for angiogenesis and the metabolic response (Whitehouse and Manzon 2019). ...
Hypoxia is a lack of required oxygen to meet the metabolic demands of living organisms. Cellular hypoxia occurs when the molecular oxygen, essential to maintain sufficient adenosine triphosphate (ATP) levels for normal physiological function, surpasses the vascular supply. Tissue hypoxia can arise during a range of diseases. As molecular oxygen is a crucial metabolic energy source for all living organisms, animals manage the intracellular oxygen levels to sustain homeostasis, with the upregulation of genes that improve tissue perfusion and anaerobic ATP creation via glycolysis. This is facilitated by the hypoxia-inducible factors (HIFs). Hypoxia-inducible factor 1α (hif-1a) is the core regulator of the hypoxia response and plays a crucial role in the cellular/molecular response to hypoxic stress by regulating the transcription of target genes. In the present study, hif-1a cDNA was identified and cloned from cobia (Rachycentron canadum), using rapid amplification of cDNA ends (RACE). The hif-1a and downstream mRNA expression levels in various tissues were then determined. The full length of hif-1a cDNA is 3642 bp, with a 2292 bp open reading frame (ORF), a 5′ non-coding region (5′-UTR) of 293 bp, 3′ non-coding region (3′-UTR) of 1057 bp, and encoding 764 amino acids. The encoded protein contains the basic helix-loop-helix domain (amino acid 22–77), PER-Arnt-SIM domain (amino acid 88–154 and 230–296), and the PAS-associated C-terminal domain (amino acid 302–345). hif-1a mRNA expression was detected in nine tissues, with the highest expression observed in the liver, and the lowest expression in the intestine and spleen. hif-1a, erythropoietin (epo), and vascular endothelial growth factor (vegf) gene expressions were analyzed in the gill, intestine, liver, and muscle under hypoxic stress. In the gills, hif-1a expression was significantly increased at all hypoxia time points as well as in the liver. Erythropoietin (epo) and vascular endothelial growth factor (vegf) showed similar trends, with a significant decrease followed by a significant increase. In the muscle, the expression of all three genes was higher than the control group after hypoxic stress. These results indicate that the expression patterns of hif-1a and related genes after hypoxic stress are tissue-specific and play an essential role in cobia’s response to hypoxia.
... Multiple gain-and loss-of-function experimental platforms in our study consistently supported an impact of Cdc42 on EGFR-MAPK pathway. EGFR signaling possesses a foundationally conserved role in regulating gut development and cell proliferation in lower (86)(87)(88)(89)(90)(91)(92) and higher eukaryotic species (93,94). The requirement of EGF initiated signaling for epithelial survival and renewal is extensively documented (48,(95)(96)(97)(98), and is proposed to keep Lgr5+ ISCs in a constitutively active state (3). ...
The regulatory mechanisms enabling the intestinal epithelium to maintain a high degree of regenerative capacity during mucosal injury remain unclear. Ex vivo survival and clonogenicity of intestinal stem cells (ISCs) strictly required Cdc42-mediated growth response and Cdc42-deficient enteroids undergo rapid apoptosis. Mechanistically, Cdc42 engaging with EGFR was required for EGF-stimulated receptor-mediated endocytosis and sufficient to promote MAPK signaling. Proteomics and kinase analysis revealed that a physiological, but non-conventionally, spliced Cdc42 variant 2 (V2), exhibited stronger MAPK-activating capability. Human CDC42-V2 is transcriptionally elevated in some colon tumor tissues. Accordingly, mice engineered to overexpress Cdc42-V2 in intestinal epithelium showed elevated MAPK signaling, enhanced regeneration, and reduced mucosal damage in response to irradiation. Overproducing Cdc42-V2 specifically in mouse ISCs enhanced intestinal regeneration following injury. Thus, the intrinsic Cdc42-MAPK program is required for intestinal epithelial regeneration while elevating this signaling cascade is capable of initiating protection from genotoxic injury.
... In this process, hypoxia inducible factor 1α (HIF-1α) and epidermal growth factor receptor (EGFR) are involved. Our previous studies have shown the presence of HIF-1α and EGFR in the respiratory part of intestine in Corydoras aeneus [6][7][8]. The suggested process of proliferation of squamous cells could contribute to the formation of lung terrestrial vertebrates, and it was consolidated. ...
The tissue organization field theory (TOFT) presented completely new, different from the previous one, perspective of research on neoplasm processes. It implicates that secretory neuroepithelial-like cells (NECs), putative chemoreceptors, are probably responsible for the control of squamous epithelial cells proliferation in digestive tract during hypoxia in gut breathing fish (GBF). On the other hand, chemoreceptors dysfunction can lead to uncontrolled proliferation and risk of cancer development in mammals including humans. The studies on NECs like cells (signal capturing and transduction) may be crucial for understanding the processes of controlling the proliferation of squamous epithelial cells in the digestive tract of GBF fish during hypoxia states. This knowledge can contribute to the explanation of cancer processes.
The novel cancer theory named ‘the tissue organization field theory’ (TOFT) suggests that carcinogenesis is a process analogous to embryonic development, whereby organs are formed through interactions among different cell types. The suggested ‘morphological remodelling’ of the epithelium under hypoxia in gut breathing fish (GBF) has many common features with carcinogenesis. It appears that research into the relationship among epidermal growth factor receptor (EGFR), hypoxia inducible factor (HIF) as well as hypoxia and normoxia states in GBF fishes can be crucial in learning about the steering mechanisms of squamous epithelium proliferation, leading to a better understanding of carcinogenesis.
