TEC-mediated tRF-31R9J regulates histone lactylation and acetylation by HDAC1 to suppress hepatocyte ferroptosis and improve non-alcoholic steatohepatitis
Abstract Background Tectorigenin (TEC) is a monomer of anthocyanin, which we found exhibits hepatoprotective effects. tRNA-derived fragments (tRFs) and ferroptosis play important roles in the pathogenesis of non-alcoholic steatohepatitis (NASH). Recent discoveries have revealed that histone lactylat...
Saved in:
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2025-01-01
|
| Series: | Clinical Epigenetics |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s13148-025-01813-3 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1832585657899286528 |
|---|---|
| author | Juanjuan Zhu Xian Wu Mao Mu Quan Zhang Xueke Zhao |
| author_facet | Juanjuan Zhu Xian Wu Mao Mu Quan Zhang Xueke Zhao |
| author_sort | Juanjuan Zhu |
| collection | DOAJ |
| description | Abstract Background Tectorigenin (TEC) is a monomer of anthocyanin, which we found exhibits hepatoprotective effects. tRNA-derived fragments (tRFs) and ferroptosis play important roles in the pathogenesis of non-alcoholic steatohepatitis (NASH). Recent discoveries have revealed that histone lactylation and acetylation play a crucial role in connecting cellular metabolism and epigenetic regulation through post-translational modification of histones. However, it is unclear whether TEC improves NASH by regulating histone lactylation, acetylation and hepatocyte ferroptosis through tRFs. Results In this study, we demonstrated that TEC significantly inhibits free fatty acids-induced hepatocyte ferroptosis both in vitro and in vivo. We identified tRF-31R9J (tRF-31-R9JP9P9NH5HYD) involved in TEC regulation of ferroptosis in steatosis hepatocytes. Overexpression of tRF-31R9J suppressed hepatocyte ferroptosis and enhanced cell viability in steatosis HepG2 cells. Knockdown of tRF-31R9J partially counteracted the inhibitory effect of TEC on ferroptosis in hepatocytes. Mechanistically, tRF-31R9J recruited HDAC1 to reduce the levels of histone lactylation and acetylation modifications of the pro-ferroptosis genes ATF3, ATF4, and CHAC1, thereby inhibiting their gene expression. Conclusions This study demonstrates that TEC-mediated tRF-31R9J inhibits hepatocyte ferroptosis through HDAC1-regulated histone delactylation and deacetylation, thereby improving NASH. These discoveries offer a theoretical foundation and new strategies for the medical management of NASH. |
| format | Article |
| id | doaj-art-adf55c901ee141fd96107ae75a29c361 |
| institution | Kabale University |
| issn | 1868-7083 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | BMC |
| record_format | Article |
| series | Clinical Epigenetics |
| spelling | doaj-art-adf55c901ee141fd96107ae75a29c3612025-01-26T12:39:14ZengBMCClinical Epigenetics1868-70832025-01-0117112110.1186/s13148-025-01813-3TEC-mediated tRF-31R9J regulates histone lactylation and acetylation by HDAC1 to suppress hepatocyte ferroptosis and improve non-alcoholic steatohepatitisJuanjuan Zhu0Xian Wu1Mao Mu2Quan Zhang3Xueke Zhao4Department of Infection, Affiliated Hospital of Guizhou Medical UniversityDepartment of Infection, Affiliated Hospital of Guizhou Medical UniversityDepartment of Infection, Affiliated Hospital of Guizhou Medical UniversityDepartment of Infection, Affiliated Hospital of Guizhou Medical UniversityDepartment of Infection, Affiliated Hospital of Guizhou Medical UniversityAbstract Background Tectorigenin (TEC) is a monomer of anthocyanin, which we found exhibits hepatoprotective effects. tRNA-derived fragments (tRFs) and ferroptosis play important roles in the pathogenesis of non-alcoholic steatohepatitis (NASH). Recent discoveries have revealed that histone lactylation and acetylation play a crucial role in connecting cellular metabolism and epigenetic regulation through post-translational modification of histones. However, it is unclear whether TEC improves NASH by regulating histone lactylation, acetylation and hepatocyte ferroptosis through tRFs. Results In this study, we demonstrated that TEC significantly inhibits free fatty acids-induced hepatocyte ferroptosis both in vitro and in vivo. We identified tRF-31R9J (tRF-31-R9JP9P9NH5HYD) involved in TEC regulation of ferroptosis in steatosis hepatocytes. Overexpression of tRF-31R9J suppressed hepatocyte ferroptosis and enhanced cell viability in steatosis HepG2 cells. Knockdown of tRF-31R9J partially counteracted the inhibitory effect of TEC on ferroptosis in hepatocytes. Mechanistically, tRF-31R9J recruited HDAC1 to reduce the levels of histone lactylation and acetylation modifications of the pro-ferroptosis genes ATF3, ATF4, and CHAC1, thereby inhibiting their gene expression. Conclusions This study demonstrates that TEC-mediated tRF-31R9J inhibits hepatocyte ferroptosis through HDAC1-regulated histone delactylation and deacetylation, thereby improving NASH. These discoveries offer a theoretical foundation and new strategies for the medical management of NASH.https://doi.org/10.1186/s13148-025-01813-3TectorigeninHistone lactylationFerroptosistRF-31-R9JP9P9NH5HYDNon-alcoholic steatohepatitis |
| spellingShingle | Juanjuan Zhu Xian Wu Mao Mu Quan Zhang Xueke Zhao TEC-mediated tRF-31R9J regulates histone lactylation and acetylation by HDAC1 to suppress hepatocyte ferroptosis and improve non-alcoholic steatohepatitis Clinical Epigenetics Tectorigenin Histone lactylation Ferroptosis tRF-31-R9JP9P9NH5HYD Non-alcoholic steatohepatitis |
| title | TEC-mediated tRF-31R9J regulates histone lactylation and acetylation by HDAC1 to suppress hepatocyte ferroptosis and improve non-alcoholic steatohepatitis |
| title_full | TEC-mediated tRF-31R9J regulates histone lactylation and acetylation by HDAC1 to suppress hepatocyte ferroptosis and improve non-alcoholic steatohepatitis |
| title_fullStr | TEC-mediated tRF-31R9J regulates histone lactylation and acetylation by HDAC1 to suppress hepatocyte ferroptosis and improve non-alcoholic steatohepatitis |
| title_full_unstemmed | TEC-mediated tRF-31R9J regulates histone lactylation and acetylation by HDAC1 to suppress hepatocyte ferroptosis and improve non-alcoholic steatohepatitis |
| title_short | TEC-mediated tRF-31R9J regulates histone lactylation and acetylation by HDAC1 to suppress hepatocyte ferroptosis and improve non-alcoholic steatohepatitis |
| title_sort | tec mediated trf 31r9j regulates histone lactylation and acetylation by hdac1 to suppress hepatocyte ferroptosis and improve non alcoholic steatohepatitis |
| topic | Tectorigenin Histone lactylation Ferroptosis tRF-31-R9JP9P9NH5HYD Non-alcoholic steatohepatitis |
| url | https://doi.org/10.1186/s13148-025-01813-3 |
| work_keys_str_mv | AT juanjuanzhu tecmediatedtrf31r9jregulateshistonelactylationandacetylationbyhdac1tosuppresshepatocyteferroptosisandimprovenonalcoholicsteatohepatitis AT xianwu tecmediatedtrf31r9jregulateshistonelactylationandacetylationbyhdac1tosuppresshepatocyteferroptosisandimprovenonalcoholicsteatohepatitis AT maomu tecmediatedtrf31r9jregulateshistonelactylationandacetylationbyhdac1tosuppresshepatocyteferroptosisandimprovenonalcoholicsteatohepatitis AT quanzhang tecmediatedtrf31r9jregulateshistonelactylationandacetylationbyhdac1tosuppresshepatocyteferroptosisandimprovenonalcoholicsteatohepatitis AT xuekezhao tecmediatedtrf31r9jregulateshistonelactylationandacetylationbyhdac1tosuppresshepatocyteferroptosisandimprovenonalcoholicsteatohepatitis |