by Hae Rim Jung, Jeonghwan Lee, Seung-Pyo Hong, Nayeon Shin, Ara Cho, Dong-Jin Shin, Jin Woo Choi, Jong-Il Kim, Jung Pyo Lee, Sung-Yup Cho
Abstract:
Abstract Kidney fibrosis is a major mechanism underlying chronic kidney disease (CKD). N 6 -methyladenosine (m 6 A) RNA methylation is associated with organ fibrosis. We investigated m 6 A profile alterations and the inhibitory effect of RNA methylation in kidney fibrosis in vitro (TGF-β-treated HK-2 cells) and in vivo (unilateral ureteral obstruction [UUO] mouse model). METTL3-mediated signaling was inhibited using siRNA in vitro or the METTL3-specific inhibitor STM2457 in vivo and in vitro. In HK-2 cells, METTL3 protein levels increased in a dose- and time-dependent manner along with an increase in the cellular m 6 A levels. In the UUO model, METTL3 expression and m 6 A levels were significantly increased. Transcriptomic and m 6 A profiling demonstrated that epithelial-to-mesenchymal transition- and inflammation-related pathways were significantly associated with RNA m 6 A methylation. Genetic and pharmacologic inhibition of METTL3 in HK-2 cells decreased TGF-β-induced fibrotic marker expression. STM2457-induced inhibition of METTL3 attenuated the degree of kidney fibrosis in vivo. Furthermore, METTL3 protein expression was significantly increased in the tissues of CKD patients with diabetic or IgA nephropathy. Therefore, targeting alterations in RNA methylation could be a potential therapeutic strategy for treating kidney fibrosis.
Reference:
Hae Rim Jung, Jeonghwan Lee, Seung-Pyo Hong, Nayeon Shin, Ara Cho, Dong-Jin Shin, Jin Woo Choi, Jong-Il Kim, Jung Pyo Lee, Sung-Yup ChoTargeting the m6A RNA methyltransferase METTL3 attenuates the development of kidney fibrosisIn Experimental & Molecular Medicine, volume 56, 2024.
Bibtex Entry:
@article{jung_targeting_2024, title = {Targeting the {m6A} {RNA} methyltransferase {METTL3} attenuates the development of kidney fibrosis}, volume = {56}, issn = {2092-6413}, url = {https://www.nature.com/articles/s12276-024-01159-5}, doi = {10.1038/s12276-024-01159-5}, abstract = {Abstract Kidney fibrosis is a major mechanism underlying chronic kidney disease (CKD). N 6 -methyladenosine (m 6 A) RNA methylation is associated with organ fibrosis. We investigated m 6 A profile alterations and the inhibitory effect of RNA methylation in kidney fibrosis in vitro (TGF-β-treated HK-2 cells) and in vivo (unilateral ureteral obstruction [UUO] mouse model). METTL3-mediated signaling was inhibited using siRNA in vitro or the METTL3-specific inhibitor STM2457 in vivo and in vitro. In HK-2 cells, METTL3 protein levels increased in a dose- and time-dependent manner along with an increase in the cellular m 6 A levels. In the UUO model, METTL3 expression and m 6 A levels were significantly increased. Transcriptomic and m 6 A profiling demonstrated that epithelial-to-mesenchymal transition- and inflammation-related pathways were significantly associated with RNA m 6 A methylation. Genetic and pharmacologic inhibition of METTL3 in HK-2 cells decreased TGF-β-induced fibrotic marker expression. STM2457-induced inhibition of METTL3 attenuated the degree of kidney fibrosis in vivo. Furthermore, METTL3 protein expression was significantly increased in the tissues of CKD patients with diabetic or IgA nephropathy. Therefore, targeting alterations in RNA methylation could be a potential therapeutic strategy for treating kidney fibrosis.}, language = {en}, number = {2}, urldate = {2024-12-02}, journal = {Experimental & Molecular Medicine}, author = {Jung, Hae Rim and Lee, Jeonghwan and Hong, Seung-Pyo and Shin, Nayeon and Cho, Ara and Shin, Dong-Jin and Choi, Jin Woo and Kim, Jong-Il and Lee, Jung Pyo and Cho, Sung-Yup}, month = feb, year = {2024}, pages = {355--369}, file = {Volltext:C:\Users\lovis\Zotero\storage\UNMKFCZN\Jung et al. - 2024 - Targeting the m6A RNA methyltransferase METTL3 att.pdf:application/pdf}, }