Involvement of Yes-Associated Protein 1 Activation in the Matrix Degradation of Human-Induced-Pluripotent-Stem-Cell-Derived Chondrocytes Induced by T-2 Toxin and Deoxynivalenol Alone and in Combination
T-2 toxin and deoxynivalenol (DON) are two prevalent mycotoxins that cause cartilage damage in Kashin-Beck disease (KBD). Cartilage extracellular matrix (ECM) degradation in chondrocytes is a significant pathological feature of KBD. It has been shown that the Hippo pathway is involved in cartilage ECM degradation. This study aimed to examine the effect of YAP, a major regulator of the Hippo pathway, on the ECM degradation in the hiPS-derived chondrocytes (hiPS-Ch) model of KBD. The hiPS-Ch injury models were established via treatment with T-2 toxin/DON alone or in combination. We found that T-2 toxin and DON inhibited the proliferation of hiPS-Ch in a dose-dependent manner; significantly increased the levels of YAP, SOX9, and MMP13; and decreased the levels of COL2A1 and ACAN (all p values < 0.05). Immunofluorescence revealed that YAP was primarily located in the nuclei of hiPS-Ch, and its expression level increased with toxin concentrations. The inhibition of YAP resulted in the dysregulated expression of chondrogenic markers (all p values < 0.05). These findings suggest that T-2 toxin and DON may inhibit the proliferation of, and induce the ECM degradation, of hiPS-Ch mediated by YAP, providing further insight into the cellular and molecular mechanisms contributing to cartilage damage caused by toxins.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2024 |
|---|---|
| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:25 |
|---|---|
| Enthalten in: |
International journal of molecular sciences - 25(2024), 2 vom: 10. Jan. |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Liu, Li [VerfasserIn] |
|---|
| Links: |
|---|
| Themen: |
Adaptor Proteins, Signal Transducing |
|---|
| Anmerkungen: |
Date Completed 24.01.2024 Date Revised 01.02.2024 published: Electronic Citation Status MEDLINE |
|---|
| doi: |
10.3390/ijms25020878 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM367464365 |
|---|
| LEADER | 01000caa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM367464365 | ||
| 003 | DE-627 | ||
| 005 | 20240202232154.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 240123s2024 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.3390/ijms25020878 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1278.xml |
| 035 | |a (DE-627)NLM367464365 | ||
| 035 | |a (NLM)38255951 | ||
| 035 | |a (PII)878 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Liu, Li |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Involvement of Yes-Associated Protein 1 Activation in the Matrix Degradation of Human-Induced-Pluripotent-Stem-Cell-Derived Chondrocytes Induced by T-2 Toxin and Deoxynivalenol Alone and in Combination |
| 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 24.01.2024 | ||
| 500 | |a Date Revised 01.02.2024 | ||
| 500 | |a published: Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a T-2 toxin and deoxynivalenol (DON) are two prevalent mycotoxins that cause cartilage damage in Kashin-Beck disease (KBD). Cartilage extracellular matrix (ECM) degradation in chondrocytes is a significant pathological feature of KBD. It has been shown that the Hippo pathway is involved in cartilage ECM degradation. This study aimed to examine the effect of YAP, a major regulator of the Hippo pathway, on the ECM degradation in the hiPS-derived chondrocytes (hiPS-Ch) model of KBD. The hiPS-Ch injury models were established via treatment with T-2 toxin/DON alone or in combination. We found that T-2 toxin and DON inhibited the proliferation of hiPS-Ch in a dose-dependent manner; significantly increased the levels of YAP, SOX9, and MMP13; and decreased the levels of COL2A1 and ACAN (all p values < 0.05). Immunofluorescence revealed that YAP was primarily located in the nuclei of hiPS-Ch, and its expression level increased with toxin concentrations. The inhibition of YAP resulted in the dysregulated expression of chondrogenic markers (all p values < 0.05). These findings suggest that T-2 toxin and DON may inhibit the proliferation of, and induce the ECM degradation, of hiPS-Ch mediated by YAP, providing further insight into the cellular and molecular mechanisms contributing to cartilage damage caused by toxins | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a DON | |
| 650 | 4 | |a Kashin–Beck disease | |
| 650 | 4 | |a T-2 toxin | |
| 650 | 4 | |a YAP | |
| 650 | 4 | |a hiPSCs | |
| 650 | 7 | |a T-2 Toxin |2 NLM | |
| 650 | 7 | |a I3FL5NM3MO |2 NLM | |
| 650 | 7 | |a deoxynivalenol |2 NLM | |
| 650 | 7 | |a JT37HYP23V |2 NLM | |
| 650 | 7 | |a YAP-Signaling Proteins |2 NLM | |
| 650 | 7 | |a Transcription Factors |2 NLM | |
| 650 | 7 | |a Adaptor Proteins, Signal Transducing |2 NLM | |
| 650 | 7 | |a Trichothecenes |2 NLM | |
| 700 | 1 | |a Liu, Huan |e verfasserin |4 aut | |
| 700 | 1 | |a Meng, Peilin |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Yanan |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Feng'e |e verfasserin |4 aut | |
| 700 | 1 | |a Jia, Yumeng |e verfasserin |4 aut | |
| 700 | 1 | |a Cheng, Bolun |e verfasserin |4 aut | |
| 700 | 1 | |a Lammi, Mikko J |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Feng |e verfasserin |4 aut | |
| 700 | 1 | |a Guo, Xiong |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t International journal of molecular sciences |d 2008 |g 25(2024), 2 vom: 10. Jan. |w (DE-627)NLM185552161 |x 1422-0067 |7 nnns |
| 773 | 1 | 8 | |g volume:25 |g year:2024 |g number:2 |g day:10 |g month:01 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.3390/ijms25020878 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 25 |j 2024 |e 2 |b 10 |c 01 | ||