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LncRNA TTN-AS1 exacerbates extracellular matrix accumulation via miR-493-3p/FOXP2 axis in diabetic nephropathy

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Abstract

Diabetic nephropathy (DN), a common cause of chronic renal failure and end-stage renal disease, leads to a high mortality. However, the role of TTN-AS1 in extracellular matrix (ECM) accumulation during DN remains unclear. In our study, TTN-AS1 exhibited high expression in high glucose-treated mesangial cells, and TTN-AS1 silencing alleviated high glucose-induced ECM accumulation in mesangial cells. Additionally, animal study revealed that TTN-AS1 was upregulated in renal tissues of DN rats, and TTN-AS1 knockdown mitigated renal injury of DN rats. Mechanistically, TTN-AS1 was validated to bind to miR-493-3p, and miR-493-3p targeted forkhead box P2 (FOXP2) 3′untranslated region in mesangial cells. TTN-AS1 interacted with miR-493-3p to upregulate FOXP2 in vitro and in vivo. Moreover, FOXP2 overexpression counteracted the effects of TTN-AS1 silencing on the ECM accumulation. In conclusion, TTN-AS1 exacerbated ECM accumulation via the miR‐493-3p/FOXP2 axis during DN development. This research may provide a potential new direction for DN treatment.

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Authors and Affiliations

  1. Department of Nephrology, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430014, Hubei, People’s Republic of China

    Lin Jia, Wenzhe Wang, Hui Liu, Fan Zhu & Yunfang Huang

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  1. Lin Jia
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  2. Wenzhe Wang
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  3. Hui Liu
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  4. Fan Zhu
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  5. Yunfang Huang
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Correspondence to Yunfang Huang.

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Corresponding editor: Upendra Nongthomba

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Jia, L., Wang, W., Liu, H. et al. LncRNA TTN-AS1 exacerbates extracellular matrix accumulation via miR-493-3p/FOXP2 axis in diabetic nephropathy. J Genet 102, 11 (2023). https://doi.org/10.1007/s12041-022-01397-4

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  • DOI: https://doi.org/10.1007/s12041-022-01397-4

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