Expression of early growth response factor-1 in rats with cerulein-induced acute pancreatitis and its significance

AIM： To observe the expressions of early growth response factor-1 （Egr-1） and tissue factor （TF） in rats with cerulein-induced acute pancreatitis and to explore its significance. METHODS： A large dose of cerulein was used to create the experimental acute pancreatitis model in rats. The changes of Egr-1 mRNA and protein in rats were observed during 30 min to 4 h after the treatment and immunohistochemical method was used to observe the localized expression of Egr-1 in tissues. In addition to the mRNA expression of Egr-1 target gene, TF was also observed. A blank control group, and a bombesinadministered group were used for comparison. RESULTS： Alter the stimulation of a large dose of cerulein, the rats showed typical inflammatory changes of acute pancreatitis. Thirty minutes alter the stimulation, the mRNA expression of Egr-1 in the pancreatic tissue reached its peak and then declined, while the expression of Egr-1 protein reached its peak 2 h after the stimulation. Histologically, 2 h after the stimulation, almost all pancreatic acinar cells had the expression of Egr-1 protein, which was focused in the nuclei. The mRNA expression of TF occurred 1 h after the stimulation and gradually increased within 4 h. However, a large dose of bombesin only stimulated the pancreatic tissue to produce a little mRNA expression of Egr-1 and no mRNA expression of Egr-1 protein and TF. CONCLUSION： Egr-1 as a pro-inflammatory transcription factor may play an important role in the pathogenesis of acute pancreatitis by modulating the expression of TF.

Growth response of broom (Cytisus scoparius) growing with and without radiata pine (Pinus radiata) seedlings to different P levels in soils

A study was carried out to test the effects of three rates of TSP （triple superphosphate） （0, 50, and 100 mg·kg^-1 P） on growth of broom with and without radiata pine seedlings and to determine the relationships between P concentrations in the broom shoot and dry matter yields with soil plant-available P （Bray-2 P）. A bulk sample of soil was collected from Kaweka forest at soil depth of 0-10 cm, in New Zealand on March 11, 2001. The forest area was not supplied with fertiliser at least 30 years. The results show that TSP application increased P avail- ability in the soil. The P availability concentration in soil of broom with radiata pine seedlings was higher than that in soil of broom alone. Bray-2 P concentrations had a significant logarithmic relationship with Pcon- centrations of broom shoot and an exponential relationship with dry matter weight of whole broom plant.

Growth Responses of Young Slash Pine (Pinus elliottii Engelm.) to N, P and K Fertilizers in Red-Yellow Soil in Jiangxi Province, China

During 1991~1995, the growth responses of young slash pine to N, P and K fertilizers and rational rate and ratio of fertilizers in yellow-red soil at Fengshushan Forest Farm, Jiangxi Province were studied. N fertilizer decreased the growth of slash pine, while P not only significantly improved the increment of bottom diameter, height and crown diameter, but also caused earlier canopy closure of the stand. It also had a sustainable effect in the next two years. Slash pine had the most significant response to the treatment of 200 kg P2O5 ha-1, in which tree height, bottom diameter and crown diameter (EW and SN) were increased by 22%, 35%, 20% and 18% in 1994, 21%, 25%, 10% and 10% in 1995, respectively, compared to the control.Although there was no remarkable response to K fertilizer, good growth response to the application of 100 kg P2O5 plus 100 kg K2O ha-1 existed and tree height, bottom diameter and crown diameter (EW and SN)were increased by 31%, 14%, 23% and 21%, respectively, in 1993, compared to the control.

Global qualitative analysis of new Monod type chemostat model with delayed growth response and pulsed input in polluted environment

In this paper, we consider a new Monod type chemostat model with time delay and impulsive input concentration of the nutrient in a polluted environment. Using the discrete dynamical system determined by the stroboscopic map, we obtain a ＂microorganism-extinction＂ periodic solution. Further, we establish the sufficient conditions for the global attractivity of the microorganism-extinction periodic solution. Using new computational techniques for impulsive and delayed differential equation, we prove that the system is permanent under appropriate conditions. Our results show that time delay is ＂profitless＂.

Early Growth Response Gene-1 Deficiency Interrupts TGFβ1 Signaling Activation and Aggravates Neurodegeneration in Experimental Autoimmune Encephalomyelitis Mice

Early growth response protein 1(Egr-1)triggers the transcription of many genes involved in cell growth,differentiation,synaptic plasticity,and neurogenesis.However,its mechanism in neuronal survival and degeneration is still poorly understood.This study demonstrated that Egr-1 was down-regulated at mRNA and protein levels in the central nervous system(CNS)of experimental autoimmune encephalomyelitis(EAE)mice.Egr-1 knockout exacerbated EAE progression in mice,as shown by increased disease severity and incidence;it also aggravated neuronal apoptosis,which was associated with weakened activation of the BDNF/TGFβ1/MAPK/Akt signaling pathways in the CNS of EAE mice.Consistently,Egr-1 siRNA promoted apoptosis but mitigated the activation of BDNF/TGFβ1/MAPK/Akt signaling in SH-SY5Y cells.Our results revealed that Egr-1 is a crucial regulator of neuronal survival in EAE by regulating TGFβ1-mediated signaling activation,implicating the important role of Egr-1 in the pathogenesis of multiple sclerosis as a potential novel therapy target.

MiR-551b-5p Contributes to Pathogenesis of Vein Graft Failure via Upregulating Early Growth Response-1 Expression

Background： Vein graft failure （VGF） is a serious complication of coronary artery bypass graft, although the mechanism remains unclear. The study aimed to investigate the effects of microRNAs （miRNAs） on the endothelial dysfunction involved in VGF. Methods： Human umbilical vein endothelial cells （HUVECs） were subjected to mechanical stretch stimulation to induce endothelial dysfunction. Genome-wide transcriptome profiling was performed using the Human miRNA OneArray＂ V4 （PhalanxBio Inc., San Diego, USA）. The miRNA-messenger RNA （mRNA） network was investigated using gene ontology and Kyoto Encyclopedia of Genes and Genomes. The miR-55 1b-5p mimic and inhibitor were applied to regulate miR-55 lb-5p expression in the HUVECs. The 5-ethynyl-2＇-deoxyuridine assay, polymerase chain reaction （PCR）, and Western blotting （WB） were used to assess HUVECs proliferation, mRNA expression, and protein expression, respectively. The vein graft model was established in early growth response （Egr）-I knockout （KO） mice and wide-type （WT） C57BL/6J mice for pathological and immunohistochemical analysis. Endothelial cells isolated from the veins of WT and Egr-1 KO mice were subjected to mechanical stretch stimulation; PCR and WB were conducted to confirm the regulatory effect of Egr- 1 on Intercellular adhesion molecule （loam-1）. One-way analysis of variance and independent t-test were performed for data analysis. Results： Thirty-eight rniRNAs were differentially expressed in HUVECs after mechanical stretch stimulation. The bioinforrnatics analysis revealed that Egr-1 might be involved in VGF and was a potential target gene of miR-551b-5p. The mechanical stretch stimulation increased miR-55 1b-5p expression by 2.93 ± 0.08 told （t= 3.07, P 〈 0.05）, compared with the normal HUVECs. Transfection with the miR-551b-5p mimic or inhibitor increased expression of miR-551b-5p by 793.1 ± 171.6 fold （t = 13.84, P 〈 0.001） or decreased by 26.3% ± 2.4% （t= 26.39, P 〈 0.05） in the HUVECs, respectively. HUVECs proliferation and EGR-I mRNA expression were significantly suppressed by inhibiting miR-551b-5p expression （P 〈 0.05）. The lumens of the vein grafts in the Egr-1 KO mice were wider than that in the WT mice. lcam-I expression was suppressed significantly in the Egr-1 KO vein grafts （P 〈 0.05）. Conclusions： Increased miR-55 1b-5p expression leads to endothelial dysfunction by upregulating Egr-1 expression. EGR-1 KO can improve the function of a grafted vein through suppressing loam-1.

Lipocalin-2-Mediated Insufficient Oligodendrocyte Progenitor Cell Remyelination for White Matter Injury After Subarachnoid Hemorrhage via SCL22A17 Receptor/Early Growth Response Protein 1 Signaling

Insufficient remyelination due to impaired oligodendrocyte precursor cell(OPC)differentiation and maturation is strongly associated with irreversible white matter injury(WMI)and neurological deficits.We analyzed whole transcriptome expression to elucidate the potential role and underlying mechanism of action of lipocalin-2(LCN2)in OPC differentiation and WMI and identified the receptor SCL22A17 and downstream transcription factor early growth response protein 1(EGR1)as the key signals contributing to LCN2-mediated insufficient OPC remyelination.In LCN-knockdown and OPC EGR1 conditional-knockout mice,we discovered enhanced OPC differentiation in developing and injured white matter(WM);consistent with this,the specific inactivation of LCN2/SCl22A17/EGR1 signaling promoted remyelination and neurological recovery in both atypical,acute WMI due to subarachnoid hemorrhage and typical,chronic WMI due to multiple sclerosis.This potentially represents a novel strategy to enhance differentiation and remyelination in patients with white matter injury.

Transcription factor EGR-1 inhibits growth of hepatocellular carcinoma and esophageal carcinoma cell lines

AIM: The transcription factor EGR-1 (early growth response gene-1) plays an important role in cell growth, differentiation and development. It has identified that EGR-1 has significant transformation suppression activity in some neoplasms, such as fibrosarcoma, breast carcinoma. This experiment was designed to investigate the role of egr-1 in the cancerous process of hepatocellular carcinoma (HCC) and esophageal carcinoma (EC), and then to appraise the effects of EGR-1 on the growth of these tumor cells. METHODS: Firstly, the transcription and expression of egr-1 in HCC and EC, paracancerous tissues and their normal counterpart parts were detected by in situ hybridization and immunohistochemistry, with normal human breast and mouse brain tissues as positive controls. Egr-1 gene was then transfected into HCC (HHCC, SMMC7721) and EC (ECa109) cell lines in which no egr-1 transcription and expression were present. The cell growth speed, FCM cell cycle, plate clone formation and tumorigenicity in nude mice were observed and the controls were the cell lines transfected with vector only. RESULTS: Little or no egr-1 transcription and expression were detected in HCC, EC and normal liver tissues. The expression of egr-1 were found higher in hepatocellular paracancerous tissue (transcription level P=0.000; expression level P=0.143, probably because fewer in number of cases) and dysplastic tissue of esophageal cancer (transcription level P=0.000; expression level P=0.001). The growth rate of egr-1-transfected HHCC (HCC cell line) cells and ECa109 (EC cell line) cells was much slower than that of the controls. The proportion of S phase cell, clone formation and tumorigenicity were significantly lower than these of the controls' (decreased 45.5% in HHCC cells and 34.1% in ECa109 cells; 46.6% and 41.8%; 80.4% and 72.6% respectively). There were no obvious differences between SMMC7721 (HCC) egr-1-transfected cells and the controls with regard to the above items. CONCLUSION: The decreased expression of egr-1 might play a role in the dysregulation of normal growth in the cancerous process of HCC and EC. Egr-1 gene of transfected HHCC and ECa109 cells showed obvious suppression of the cell growth and malignant phenotypes, but no suppression in SMMC7721 (HCC cell line) cells.

Growth changes and tissues anatomical characteristics of giant reed(Arundo donax L.) in soil contaminated with arsenic,cadmium and lead

A greenhouse experiment was conducted to elucidate the growth changes and tissues anatomical characteristics of giant reed(Arundo donax L.),a perennial rhizomatous grass,which was cultivated for 70 d in soils contaminated with As,Cd and Pb.The results show that giant reed rapidly grows with big biomass of shoots in contaminated soil,possessing strong metal-tolerance with limited metal translocation from roots to shoots.When As,Cd and Pb concentrations in the soil are less than 254,76.1 and 1 552 mg/kg,respectively,plant height and dried biomass are slightly reduced,the accumulation of As,Cd and Pb in shoots of giant reed is low while metal concentration in roots is high,and the anatomical characteristics of stem tissues are thick and homogeneous according to SEM images.However,plant height and dried biomass are significantly reduced and metal concentration in plant shoots and roots are significantly increased(P<0.05),the stems images become heterogeneous and the secretion in vascular bundles increases significantly when As,Cd and Pb concentrations in the soil exceed 334,101 and 2 052 mg/kg,respectively.The giant reed is a promising,naturally occurring plant with strong metal-tolerance,which can be cultivated in soils contaminated with multiple metals for ecoremediation purposes.

Ecological functions of ciliated protozoa in marine ecosystem： effects of ammonium on the population growth of Euplotes vannus

The effects of ammonium on the population growth of the marine ciliate, Euplotes vannus, were examined using ecotoxicological method, h is showed that ammonium exerts inhibitory effects on the growth of the ciliate populations in a concentration-dependent way. Statistical analvsis reveals that the population growth dynamics exposed to ammoniunt-N concentration over 100mg/L are significantly different from that in the control at P 〈 0.05 level. Linear regression determined that the 24h, 36h, 48h, 60h, 72h and 84h IC50 values of ammonium-N are 19.68, 201.51, 167.49, 47.86, 50.43 and 43.11 concentration over 100mg/L, respectively （ P 〈 0.05; pH 8.2; salinity 28 ppt; temperature, 25℃ ）. The results indicate that the tolerance to ammonium in E. vannus is considerably higher than that of the larvae or juveniles of some metozoa, such as cuhured prawns and oysters. Therefore, it is believed that the high tolerance to ammonium is necessary for eiliated protozoa to play positive roles in maintaining and improving water quality in marine ecosystems, especially in the intensive aquacuhure waters with high-level ammonium. In addition, the correlation between /C50 values and exposure time was discussed.

Control of tendon cell fate in the embryonic limb: A molecular perspective

The molecular cascade underlying tendon formation starts when progenitor cells begin to express the Scleraxis(Scx)gene.Scx knockout mice develop some but not all tendons,suggesting that additional factors are necessary for tendon commitment,maintenance,and differentiation.Other transcription factors,such as Mohawk(Mkx)or early growth response(Egr),maintain Scx expression and extracellular matrix formation during fibrillogenesis.The inhibition of wingless and int-related protein signaling is necessary and sufficient to induce the expression of Scx.Once the commitment of tenogenic lineage occurs,transforming growth factor-beta(TGFβ)induces the Scx gene expression,becoming involved in the maintenance of tendon cell fate.From this point of view,we discussed two phases of the tenogenic process during limb development:dependent and independent of mechanical forces.Finally,we highlight the importance of understanding embryonic tendon development to improve therapeutic strategies in regenerative medicines for tendons.

Effect of adrenomedullin on neuron apoptosis, infarction volume and expression of Egr-1 mRNA after focal ischemia-reperfusion in rats

Objective To observe the influence of adrenomedullin （ADM） on neuron apoptosis, infarction volume of brain, and the expression of early growth response 1 （Egr-1） mRNA in ischemia-reperfusion rats. Methods The arteria cerebri media was tied for 2 h to construct the ischemia model. Infarction volume was detected by triphenltetrazolium chloride （T＇I＇C） staining, neuronal apoptosis and necrosis was detected with terminal deoxynucleotidyl transferase nick labeling （TUNEL） method, and the Egr-1 mRNA expression was examined by in situ hybridization （ISH）. Results Infarction volume after ischemia-reperfusion is （269 ± 20） mm^3. Infarction volume after injection of ADM through different ways are femoral vein （239 ± 17） mm^3 （decreased by 11.2%）, arteria carotis （214 ± 14） mm^3 （by 20.4%） and lateral cerebral ventricle （209 ± 13） mm^3 （by 22.3%）, respectively. The results indicate that injecting ADM through arteria carotis and lateral cerebral ventricle is much more effective than it through femoral vein （P 〈 0.05）. The TUNEL-positive cells in cerebral cortex or hippocampus are few in the sham operation group, but much more in the ischemia-reperfusion group. After being supplied with ADM, especially through arteria carotis interna or lateral cerebral ventricle way, the TUNEL-positive cells decreased obviously. Expression of Egr- 1 mRNA was low in the cerebral cortex of the sham operation group rats, enhanced in the ischemia and reperfusion group rats, and enhanced markedly after treatment with ADM, especially through arteria carotis interna or lateral cerebral ventricle way （P 〈 0.01）. Conclusion Injection of ADM through different ways could alleviate neural dysfunction, decrease neuron apoptosis and brain infarction volume, and increase the expression of Egr- 1 mRNA.

Involvement of MAPK/ERK kinase-ERK pathway in exogenous bFGF-induced Egr-1 binding activity enhancement in anoxia-reoxygenation injured astrocytes

Objective Intravenous administration of basic fibroblast growth factor （bFGF） is effective to reduce the volume of cerebral infract due to ischemia. This study was designed to investigate the molecular mechanism, especially the signal transduction pathways, involved in this protective role of bFGF. Methods Anoxia-reoxygenation treated atrocytes were used to study the role of mitogen-activated protein kinase/extracellular signal-regulated kinase kinase （MAPK/ERK kinase, MEK）-ERK signaling pathway after exogenous bFGF administration by Western blot. Electrophoretic mobile shift assay was used to detect the binding activity of early growth response factor-1 （Egr-1）, an important transcription factor for endogenous bFGF. Results bFGF could protect some signal transduction proteins from the oxygen-derived free radicals induced degradation. ERK1/2 was activated and involved in Egr-1 binding activity enhancement induced by exogenous bFGF. Conclusion MEK-ERK MAPK cascade may be an important signal transduction pathway contributed to bFGF induced enhancement of Egr-1 binding activity in anoxia-reoxygenation injured astrocytes.

Experimental and clinic-opathologic study on the relationship between transcription factor Egr-1 and esophageal carcinoma

AIM: To observe the growth suppression effect of exogenous introduction of early growth response gene-1 (Egr-1 gene) on esophageal carcinoma tissue as well as on esophageal carcinoma cell line Eca109 and to explore the potential application of Egr-1 gene in gene therapy of tumor. METHODS: Eukaryotic expression vector of PCMV-Egr-1 plasmid was introduced into Eca109 cell line which expressed no Egr-1 protein originally with lipofectamine transfection method. The introduction and expression of PCMV-Egr-1 plasmid into Eca109 cell line was confirmed by G418 selection culture, PCR amplification of neogene contained in the vector, Western blot analysis and immunocytochemical analysis. The cell growth curve, soft agar colony formation rate and tumorigenicity in SCID mice were examined to demonstrate the growth suppression effect of exogenous Egr-1 gene on Eca109 cell line. The Egr-1 mRNA and Egr-1 protein were also detected in 50 surgical specimens of esophageal carcinoma by in situ hybridization and immunohistochemistry. RESULTS: Exogenous Egr-1 gene was introduced successfully into Eca109 cell line and expressed Egr-1 protein stably. The transfected Eca109 cell line grew more slowly than control Eca109 as shown by cell growth curves, the soft agar colony formation rate (4.0% vs 6.9%, P 【 0.01) and the average growth rate of tumor in SCID mice (35.5 +/- 7.6 vs 65.8 +/- 7.6, P 【 0.05). The expression level of Egr-1 mRNA and protein significantly increased in dysplastic epithelia adjacent to cancer rather than in cancer tissues (65.8% vs 20.0% by ISH and 57.9% vs 0.01). CONCLUSION: Exogenous Egr-1 gene shows the strong effect of growth inhibition in Eca109 cell line. Egr-1 in the cancer tissue shows down-regulated expression that supports the inhibited function of Egr-1 in cancer growth and suggests Egr-1 may have an important role in gene therapy of esophageal carcinoma.

Hippocampal and thalamic neuronal metabolism in a putative rat model of schizophrenia°

The transcription factor early growth response protein 3 （EGR3） is involved in schizophrenia. We developed a putative rat model of schizophrenia by transfecting lentiviral particles carrying the Egr3 gene into bilateral hippocampal dentate gyrus. We assessed spatial working memory using the Morris water maze test, and neuronal metabolite levels in bilateral hippocampus and thalamus were determined by 3.0 T proton magnetic resonance spectroscopy. Choline content was significantly greater in the hippocampus after transfection, while N-acetylaspartate and the ratio of N-acetylaspartate to creatine/phosphocreatine in the thalamus were lower than in controls. This study is the first to report evaluation of brain metabolites using 3,0 T proton magnetic resonance spectroscopy in rats transfected with Egr3, and reveals metabolic abnormalities in the hippocampus and thalamus in this putative model of schizophrenia.

Alterations of Endogenous Hormonal Levels in Plants under Drought and Salinity

The phytohormones are pivotal chemical messengers produced within the plant that regulate its growth and development, and responses to environmental stimuli. Drought and salinity are adverse environmental factors that disturb the plant hormonal balance. Accordingly, these hormonal fluctuations modify the cellular dynamic and hence they play a central role in regulating plant growth responses to abiotic stresses such as drought and salinity. The present review gives an update about the alterations of endogenous phytohormones such as abscisic acid (ABA), auxins (Aux), cytokinins (CKs), ethylene (ET), gibberellins (GAs), jasmonates (JAs), salicylic acid (SA), brassinosteroids (BRs), strigolactones (SLs) and nitric oxide (NO) that occur as part of the adaptative responses of plant against drought and salt stresses. Better understanding of the endogenous hormonal changes during the plant response to both abiotic stresses will contribute, in part, to the development of stress-tolerant plants.

Expression of Egr-1 in the liver of mice following hemorrhagic shock and resuscitation

Objective: To investigate the expression of early growth response gene-1(Egr-1) in the liver following hemorrhagic shock with or without resuscitation(HS or HSR). Methods: Mice were subjected to HS or HSR.Liver expression of Egr-1 mRNA was detected by Northern blotting.DNA binding activity of the Egr-1 protein in liver nuclear extracts(NE) was determined by electrophoretic mobility shift assay(EMSA).Western blot analysis was used to assess the induction of Egr-1 protein in the liver tissue,cytoplasma and NE. Results: Egr-1 mRNA was strongly expressed as early as 1 h after HS,and its level was decreased in the following 2.5 h but still higher than that in 1 h HS group.The Egr-1 DNA binding activity elevated in the liver NE of 2.5 h HS group and 2.5 h HS + 4 h R group,so did the Egr-1 protein in the liver and the liver NE of the same two groups.However,the maximal Egr-1 protein expression was found in the cytoplasma of liver following 2.5 h HS. Conclusion: Our data suggest that both Egr-1 mRNA and protein are strongly elevated and the binding activity of Egr-1 to its cognate DNA site is increased in the liver following HSR,indicating the increases of Egr-1 transcriptional and translational levels.This study provides evidence that Egr-1 gene is activated in the liver during HS and HSR.

Research progress of the synapsin 2 gene polymorphism in the pathogenesis of schizophrenia

Schizophrenia(SCZ)is the most common serious mental illness with a high disability rate and heavy social and family burdens.At present,there is no clear etiology and pathogenesis of schizophrenia.Studies have shown that the occurrence of schizophrenia may be related to the abnormality of the hypothalamic-pituitary-adrenal(HPA)axis.The LIM-homeobox gene 3(LHXS)and early growth response 1(EGR1)can affect pituitary function.Because the synapsin 2(SYN2)gene polymorphism regulates the activity of LHX3 and EGR1,it may cause the occurrence of schizophrenia.This article will review the possible involvement of SYN2 gene polymorphism in the pathogenesis of schizophrenia via regulating the activity of LHX3 and EGR1,then to afiect the HPA axis.

Potassium channel AKT1 is involved in the auxin-mediated root growth inhibition in Arabidopsis response to low K^+stress

The changes in external K^＋ concentration affect plant root growth. However, the molecular mechanism for perceiving a K^＋ signal to modulate root growth remains unknown. It is hypothesized that the K^＋ channel AKTI is involved in low K^＋ sensing in the Arabidopsis root and subsequent regulation of root growth. Along with the decline of external K^＋ concentration, the primary root growth of wild-type plants was gradually inhibited. However, the primary root of the akt1 mutant could still grow under low K^＋（LK） conditions. Application of NAA inhibited akt1 root growth, but promoted wild-type root growth under LK conditions. By using the ProDR5：GFP and ProPIN1：PIN1-GFP lines, we found that LK treatment reduced auxin accumulation in wild-type root tips by degrading PIN1 proteins, which did not occur in the akt1 mutant. The LK-induced PIN1 degradation may be due to the inhibition of vesicle trafficking of PIN1 proteins. In conclusion, our findings indicate that AKT1 is required for an Arabidopsis response to changes in external K^＋, and subsequent regulation of K^＋-dependent root growth by modulating PINt degradation and auxin redistribution in the root.

Heme oxygenase 1-mediated ferroptosis in Kupffer cells initiates liver injury during heat stroke

With the escalating prevalence of global heat waves,heat stroke has become a prominent health concern,leading to substantial liver damage.Unlike other forms of liver injury,heat strokeinduced damage is characterized by heat cytotoxicity and heightened inflammation,directly contributing to elevated mortality rates.While clinical assessments have identified elevated bilirubin levels as indicative of Kupffer cell dysfunction,their specific correlation with heat stroke liver injury remains unclear.Our hypothesis proposes the involvement of Kupffer cell ferroptosis during heat stroke,initiating IL-1bmediated inflammation.Using single-cell RNA sequencing of murine macrophages,a distinct and highly susceptible Kupffer cell subtype,Clec4Ft/CD206t,emerged,with heme oxygenase 1(HMOX-1)playing a pivotal role.Mechanistically,heat-induced HMOX-1,regulated by early growth response factor 1,mediated ferroptosis in Kupffer cells,specifically in the Clec4F t/CD206 t subtype(KC2),activating phosphatidylinositol 4-kinase beta and promoting PI4P production.This cascade triggered NLRP3 inflammasome activation and maturation of IL-1b.These findings underscore the critical role of targeted therapy against HMOX-1 in ferroptosis within Kupffer cells,particularly in Clec4F t/CD206 t KCs.Such an approach has the potential to mitigate inflammation and alleviate acute liver injury in the context of heat stroke,offering a promising avenue for future therapeutic interventions.