Ochratoxin A induces endoplasmic reticulum stress and fibrosis in the kidney via the HIF-1α/miR-155-5p link

Seon Ah Yang; Kyu Hyun Rhee; Hee Joon Yoo; Min Cheol Pyo; Kwang Won Lee

doi:10.1016/j.toxrep.2023.01.006

Ochratoxin A induces endoplasmic reticulum stress and fibrosis in the kidney via the HIF-1α/miR-155-5p link

Seon Ah Yang, Kyu Hyun Rhee, Hee Joon Yoo, Min Cheol Pyo, Kwang Won Lee

Research output: Contribution to journal › Article › peer-review

6 Citations (Scopus)

Abstract

Ochratoxin A (OTA) is a ubiquitous fungal toxin found in agricultural products and foods that is toxic to both humans and animals. OTA mainly affects kidney, but the mechanisms underlying OTA-induced nephrotoxicity remain not fully understood. MicroRNA (miRNA) is involved in key cellular processes. The toxic mechanism and regulatory effects of miRNAs on OTA toxicity in kidney, and particularly the role of HIFα-1/miR-155–5p on OTA-caused ER stress and fibrosis, were investigated in this study. OTA induced hypoxia-like conditions such as ER stress and fibrosis in HK-2 cells and renal tissues via modulating HIF-1α, which was followed by regulation of ER stress-related proteins (GRP78 and ATF-4), as well as fibrosis-related markers (fibronectin, α-SMA, and E-cadherin). Notably, a total of 62 miRNAs showed significant differential expression in kidney of OTA-treated mice. Under OTA exposure, HIF-1α enhanced miR-155–5p expression, causing ER stress and fibrosis in HK-2 cells. HIF-1α knockdown decreased OTA-induced miR-155–5p expression as well as ER stress and fibrotic responses, whereas miR-155–5p overexpression restored this. Our data suggest that OTA enhances ER stress and fibrosis in the kidney through upregulating the HIF-1α/miR-155–5p link.

Original language	English
Pages (from-to)	133-145
Number of pages	13
Journal	Toxicology Reports
Volume	10
DOIs	https://doi.org/10.1016/j.toxrep.2023.01.006
Publication status	Published - 2023 Jan

Bibliographical note

Funding Information:
This work was supported by the National Research Foundation (NRF) grant funded by the Korea government (MIST) (No. 2021R1A2C1007428). The authors thank the Korea University-CJ Food Safety Center (Seoul, Republic of Korea) for providing the equipment and facilities.

Funding Information:
This work was supported by the National Research Foundation ( NRF ) grant funded by the Korea government (MIST) (No. 2021R1A2C1007428 ). The authors thank the Korea University-CJ Food Safety Center (Seoul, Republic of Korea) for providing the equipment and facilities.

Publisher Copyright:
© 2023

Keywords

ER stress
Fibrosis
HIF-1α
Kidney
MiRNA-155–5p
Ochratoxin A

ASJC Scopus subject areas

Toxicology
Health, Toxicology and Mutagenesis

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10.1016/j.toxrep.2023.01.006

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@article{57a983a226844d91bc7a2044a39cf76f,

title = "Ochratoxin A induces endoplasmic reticulum stress and fibrosis in the kidney via the HIF-1α/miR-155-5p link",

abstract = "Ochratoxin A (OTA) is a ubiquitous fungal toxin found in agricultural products and foods that is toxic to both humans and animals. OTA mainly affects kidney, but the mechanisms underlying OTA-induced nephrotoxicity remain not fully understood. MicroRNA (miRNA) is involved in key cellular processes. The toxic mechanism and regulatory effects of miRNAs on OTA toxicity in kidney, and particularly the role of HIFα-1/miR-155–5p on OTA-caused ER stress and fibrosis, were investigated in this study. OTA induced hypoxia-like conditions such as ER stress and fibrosis in HK-2 cells and renal tissues via modulating HIF-1α, which was followed by regulation of ER stress-related proteins (GRP78 and ATF-4), as well as fibrosis-related markers (fibronectin, α-SMA, and E-cadherin). Notably, a total of 62 miRNAs showed significant differential expression in kidney of OTA-treated mice. Under OTA exposure, HIF-1α enhanced miR-155–5p expression, causing ER stress and fibrosis in HK-2 cells. HIF-1α knockdown decreased OTA-induced miR-155–5p expression as well as ER stress and fibrotic responses, whereas miR-155–5p overexpression restored this. Our data suggest that OTA enhances ER stress and fibrosis in the kidney through upregulating the HIF-1α/miR-155–5p link.",

keywords = "ER stress, Fibrosis, HIF-1α, Kidney, MiRNA-155–5p, Ochratoxin A",

author = "Yang, {Seon Ah} and Rhee, {Kyu Hyun} and Yoo, {Hee Joon} and Pyo, {Min Cheol} and Lee, {Kwang Won}",

note = "Funding Information: This work was supported by the National Research Foundation (NRF) grant funded by the Korea government (MIST) (No. 2021R1A2C1007428). The authors thank the Korea University-CJ Food Safety Center (Seoul, Republic of Korea) for providing the equipment and facilities. Funding Information: This work was supported by the National Research Foundation ( NRF ) grant funded by the Korea government (MIST) (No. 2021R1A2C1007428 ). The authors thank the Korea University-CJ Food Safety Center (Seoul, Republic of Korea) for providing the equipment and facilities. Publisher Copyright: {\textcopyright} 2023",

year = "2023",

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doi = "10.1016/j.toxrep.2023.01.006",

language = "English",

volume = "10",

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journal = "Toxicology Reports",

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AU - Yang, Seon Ah

AU - Rhee, Kyu Hyun

AU - Yoo, Hee Joon

AU - Pyo, Min Cheol

AU - Lee, Kwang Won

N1 - Funding Information: This work was supported by the National Research Foundation (NRF) grant funded by the Korea government (MIST) (No. 2021R1A2C1007428). The authors thank the Korea University-CJ Food Safety Center (Seoul, Republic of Korea) for providing the equipment and facilities. Funding Information: This work was supported by the National Research Foundation ( NRF ) grant funded by the Korea government (MIST) (No. 2021R1A2C1007428 ). The authors thank the Korea University-CJ Food Safety Center (Seoul, Republic of Korea) for providing the equipment and facilities. Publisher Copyright: © 2023

PY - 2023/1

Y1 - 2023/1

N2 - Ochratoxin A (OTA) is a ubiquitous fungal toxin found in agricultural products and foods that is toxic to both humans and animals. OTA mainly affects kidney, but the mechanisms underlying OTA-induced nephrotoxicity remain not fully understood. MicroRNA (miRNA) is involved in key cellular processes. The toxic mechanism and regulatory effects of miRNAs on OTA toxicity in kidney, and particularly the role of HIFα-1/miR-155–5p on OTA-caused ER stress and fibrosis, were investigated in this study. OTA induced hypoxia-like conditions such as ER stress and fibrosis in HK-2 cells and renal tissues via modulating HIF-1α, which was followed by regulation of ER stress-related proteins (GRP78 and ATF-4), as well as fibrosis-related markers (fibronectin, α-SMA, and E-cadherin). Notably, a total of 62 miRNAs showed significant differential expression in kidney of OTA-treated mice. Under OTA exposure, HIF-1α enhanced miR-155–5p expression, causing ER stress and fibrosis in HK-2 cells. HIF-1α knockdown decreased OTA-induced miR-155–5p expression as well as ER stress and fibrotic responses, whereas miR-155–5p overexpression restored this. Our data suggest that OTA enhances ER stress and fibrosis in the kidney through upregulating the HIF-1α/miR-155–5p link.

AB - Ochratoxin A (OTA) is a ubiquitous fungal toxin found in agricultural products and foods that is toxic to both humans and animals. OTA mainly affects kidney, but the mechanisms underlying OTA-induced nephrotoxicity remain not fully understood. MicroRNA (miRNA) is involved in key cellular processes. The toxic mechanism and regulatory effects of miRNAs on OTA toxicity in kidney, and particularly the role of HIFα-1/miR-155–5p on OTA-caused ER stress and fibrosis, were investigated in this study. OTA induced hypoxia-like conditions such as ER stress and fibrosis in HK-2 cells and renal tissues via modulating HIF-1α, which was followed by regulation of ER stress-related proteins (GRP78 and ATF-4), as well as fibrosis-related markers (fibronectin, α-SMA, and E-cadherin). Notably, a total of 62 miRNAs showed significant differential expression in kidney of OTA-treated mice. Under OTA exposure, HIF-1α enhanced miR-155–5p expression, causing ER stress and fibrosis in HK-2 cells. HIF-1α knockdown decreased OTA-induced miR-155–5p expression as well as ER stress and fibrotic responses, whereas miR-155–5p overexpression restored this. Our data suggest that OTA enhances ER stress and fibrosis in the kidney through upregulating the HIF-1α/miR-155–5p link.

KW - ER stress

KW - Fibrosis

KW - HIF-1α

KW - Kidney

KW - MiRNA-155–5p

KW - Ochratoxin A

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DO - 10.1016/j.toxrep.2023.01.006

M3 - Article

AN - SCOPUS:85146634397

SN - 2214-7500

VL - 10

SP - 133

EP - 145

JO - Toxicology Reports

JF - Toxicology Reports

ER -

Ochratoxin A induces endoplasmic reticulum stress and fibrosis in the kidney via the HIF-1α/miR-155-5p link

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

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