Hypoxia-inducible factor 1α inhibits heat stress-induced pig intestinal epithelial cell apoptosis through eif2α/ATF4/CHOP signaling
Copyright © 2024 Elsevier B.V. All rights reserved..
Unstoppable global warming and increased frequency of extreme heat leads to human and animals easier to suffer from heat stress (HS), with gastrointestinal abnormalities as one of the initial clinical symptoms. HS induces intestinal mucosal damage owing to intestinal hypoxia and hyperthermia. Hypoxia-inducible factor 1α (HIF-1α) activates numerous genes to mediate cell hypoxic responses; however, its role in HS-treated intestinal mucosa is unknown. This work aimed to explore HIF-1α function and regulatory mechanisms in HS-treated pig intestines. We assigned 10 pigs to control and moderate HS groups. Physical signs, stress, and antioxidant levels were detected, and the intestines were harvested after 72 h of HS treatment to study histological changes and HIF-1α, heat shock protein 90 (HSP90), and prolyl-4-hydroxylase 2 (PHD-2) expression. In addition, porcine intestinal columnar epithelial cells (IPEC-J2) underwent HS treatment (42 °C, 5 % O2) to further explore the functions and regulatory mechanism of HIF-1α. The results of histological examination revealed HS caused intestinal villi damage and increased apoptotic epithelial cell; the expression of HIF-1α and HSP90 increased while PHD-2 showed and opposite trend. Transcriptome sequencing analysis revealed that HS activated HIF-1 signaling. To further explore the role of HIF-1α on HS induced IPEC-J2 apoptosis, the HIF-1α was interfered and overexpression respectively, and the result confirmed that HIF-1α could inhibited cell apoptosis under HS. Furthermore, HS-induced apoptosis depends on eukaryotic initiation factor 2 alpha (eif2α)/activating transcription factor 4 (ATF4)/CCAAT-enhancer-binding protein homologous protein (CHOP) pathway, and HIF-1α can inhibit this pathway to alleviate IPEC-J2 cell apoptosis. In conclusion, this study suggests that HS can promote intestinal epithelial cell apoptosis and cause pig intestinal mucosal barrier damage; the HIF-1α can alleviate cell apoptosis by inhibiting eif2α/ATF4/CHOP signaling. These results indicate that HIF-1α plays a protective role in HS, and offers a potential target for HS prevention and mitigation.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2024 |
|---|---|
| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:924 |
|---|---|
| Enthalten in: |
The Science of the total environment - 924(2024) vom: 10. Apr., Seite 171649 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Li, Hui [VerfasserIn] |
|---|
| Links: |
|---|
| Anmerkungen: |
Date Completed 03.04.2024 Date Revised 11.04.2024 published: Print-Electronic Citation Status MEDLINE |
|---|
| doi: |
10.1016/j.scitotenv.2024.171649 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM369747046 |
|---|
| LEADER | 01000caa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM369747046 | ||
| 003 | DE-627 | ||
| 005 | 20240411232449.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 240315s2024 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1016/j.scitotenv.2024.171649 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1372.xml |
| 035 | |a (DE-627)NLM369747046 | ||
| 035 | |a (NLM)38485018 | ||
| 035 | |a (PII)S0048-9697(24)01791-1 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Li, Hui |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Hypoxia-inducible factor 1α inhibits heat stress-induced pig intestinal epithelial cell apoptosis through eif2α/ATF4/CHOP signaling |
| 264 | 1 | |c 2024 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 03.04.2024 | ||
| 500 | |a Date Revised 11.04.2024 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2024 Elsevier B.V. All rights reserved. | ||
| 520 | |a Unstoppable global warming and increased frequency of extreme heat leads to human and animals easier to suffer from heat stress (HS), with gastrointestinal abnormalities as one of the initial clinical symptoms. HS induces intestinal mucosal damage owing to intestinal hypoxia and hyperthermia. Hypoxia-inducible factor 1α (HIF-1α) activates numerous genes to mediate cell hypoxic responses; however, its role in HS-treated intestinal mucosa is unknown. This work aimed to explore HIF-1α function and regulatory mechanisms in HS-treated pig intestines. We assigned 10 pigs to control and moderate HS groups. Physical signs, stress, and antioxidant levels were detected, and the intestines were harvested after 72 h of HS treatment to study histological changes and HIF-1α, heat shock protein 90 (HSP90), and prolyl-4-hydroxylase 2 (PHD-2) expression. In addition, porcine intestinal columnar epithelial cells (IPEC-J2) underwent HS treatment (42 °C, 5 % O2) to further explore the functions and regulatory mechanism of HIF-1α. The results of histological examination revealed HS caused intestinal villi damage and increased apoptotic epithelial cell; the expression of HIF-1α and HSP90 increased while PHD-2 showed and opposite trend. Transcriptome sequencing analysis revealed that HS activated HIF-1 signaling. To further explore the role of HIF-1α on HS induced IPEC-J2 apoptosis, the HIF-1α was interfered and overexpression respectively, and the result confirmed that HIF-1α could inhibited cell apoptosis under HS. Furthermore, HS-induced apoptosis depends on eukaryotic initiation factor 2 alpha (eif2α)/activating transcription factor 4 (ATF4)/CCAAT-enhancer-binding protein homologous protein (CHOP) pathway, and HIF-1α can inhibit this pathway to alleviate IPEC-J2 cell apoptosis. In conclusion, this study suggests that HS can promote intestinal epithelial cell apoptosis and cause pig intestinal mucosal barrier damage; the HIF-1α can alleviate cell apoptosis by inhibiting eif2α/ATF4/CHOP signaling. These results indicate that HIF-1α plays a protective role in HS, and offers a potential target for HS prevention and mitigation | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Apoptosis | |
| 650 | 4 | |a Endoplasmic reticulum stress | |
| 650 | 4 | |a Heat stress | |
| 650 | 4 | |a Hypoxia-inducible factor 1α | |
| 650 | 4 | |a Pig intestinal epithelial cells | |
| 650 | 7 | |a Activating Transcription Factor 4 |2 NLM | |
| 650 | 7 | |a 145891-90-3 |2 NLM | |
| 650 | 7 | |a Eukaryotic Initiation Factor-2 |2 NLM | |
| 650 | 7 | |a Hypoxia-Inducible Factor 1, alpha Subunit |2 NLM | |
| 650 | 7 | |a Transcription Factor CHOP |2 NLM | |
| 650 | 7 | |a 147336-12-7 |2 NLM | |
| 700 | 1 | |a Zhang, Gang |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Yongqing |e verfasserin |4 aut | |
| 700 | 1 | |a Gao, Fan |e verfasserin |4 aut | |
| 700 | 1 | |a Ye, Xinyue |e verfasserin |4 aut | |
| 700 | 1 | |a Lin, Rutao |e verfasserin |4 aut | |
| 700 | 1 | |a Wen, Ming |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t The Science of the total environment |d 1972 |g 924(2024) vom: 10. Apr., Seite 171649 |w (DE-627)NLM000215562 |x 1879-1026 |7 nnns |
| 773 | 1 | 8 | |g volume:924 |g year:2024 |g day:10 |g month:04 |g pages:171649 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1016/j.scitotenv.2024.171649 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 924 |j 2024 |b 10 |c 04 |h 171649 | ||