Noncoding RNAs: Master Regulator of Fibroblast to Myofibroblast Transition in Fibrosis

Overview

Journal Int J Mol Sci

Publisher MDPI

Specialties Biochemistry
Chemistry
Molecular Biology

Date 2023 Jan 21

PMID 36675315

Authors

Huamin Zhang

Yutong Zhou

Dada Wen

Jie Wang

Affiliations

Soon will be listed here.

Abstract

Myofibroblasts escape apoptosis and proliferate abnormally under pathological conditions, especially fibrosis; they synthesize and secrete a large amount of extracellular matrix (ECM), such as α-SMA and collagen, which leads to the distortion of organ parenchyma structure, an imbalance in collagen deposition and degradation, and the replacement of parenchymal cells by fibrous connective tissues. Fibroblast to myofibroblast transition (FMT) is considered to be the main source of myofibroblasts. Therefore, it is crucial to explore the influencing factors regulating the process of FMT for the prevention, treatment, and diagnosis of FMT-related diseases. In recent years, non-coding RNAs, including microRNA, long non-coding RNAs, and circular RNAs, have attracted extensive attention from scientists due to their powerful regulatory functions, and they have been found to play a vital role in regulating FMT. In this review, we summarized ncRNAs which regulate FMT during fibrosis and found that they mainly regulated signaling pathways, including TGF-β/Smad, MAPK/P38/ERK/JNK, PI3K/AKT, and WNT/β-catenin. Furthermore, the expression of downstream transcription factors can be promoted or inhibited, indicating that ncRNAs have the potential to be a new therapeutic target for FMT-related diseases.

Citing Articles

Complement Immune System in Pulmonary Hypertension-Cooperating Roles of Circadian Rhythmicity in Complement-Mediated Vascular Pathology.

DeVaughn H, Rich H, Shadid A, Vaidya P, Doursout M, Shivshankar P Int J Mol Sci. 2024; 25(23).

PMID: 39684535 PMC: 11641342. DOI: 10.3390/ijms252312823.

Polymorphism in the Vitamin D Receptor Gene Decreases the Risk of Perianal Fistulas in Crohn's Disease.

Gisbert-Ferrandiz L, Llau J, Ortiz-Masia D, Cosin-Roger J, Macias-Ceja D, Hinojosa J Nutrients. 2024; 16(20).

PMID: 39458479 PMC: 11510363. DOI: 10.3390/nu16203485.

Rosmarinic Acid Alleviates Radiation-Induced Pulmonary Fibrosis by Downregulating the tRNA N7-Methylguanosine Modification-Regulated Fibroblast-to-Myofibroblast Transition Through the Exosome Pathway.

Zhang T, Mi J, Qin X, Ouyang Z, Wang Y, Li Z J Inflamm Res. 2024; 17:5567-5586.

PMID: 39188632 PMC: 11346487. DOI: 10.2147/JIR.S458794.

Emerging roles of non-coding RNAs in fibroblast to myofibroblast transition and fibrotic diseases.

Xing X, Rodeo S Front Pharmacol. 2024; 15:1423045.

PMID: 39114349 PMC: 11303237. DOI: 10.3389/fphar.2024.1423045.

Crosstalk of ubiquitin system and non-coding RNA in fibrosis.

Zhang H, Zhou Y, Jiang C, Jian N, Wang J Int J Biol Sci. 2024; 20(10):3802-3822.

PMID: 39113708 PMC: 11302871. DOI: 10.7150/ijbs.93644.

References

Zhu-Ge D, Yang Y, Jiang Z . Knockdown CRNDE alleviates LPS-induced inflammation injury via FOXM1 in WI-38 cells. Biomed Pharmacother. 2018; 103:1678-1687. DOI: 10.1016/j.biopha.2018.04.192. View

Wang X, Morelli M, Matarese A, Sardu C, Santulli G . Cardiomyocyte-derived exosomal microRNA-92a mediates post-ischemic myofibroblast activation both in vitro and ex vivo. ESC Heart Fail. 2020; 7(1):284-288. PMC: 7083461. DOI: 10.1002/ehf2.12584. View

Kilari S, Cai C, Zhao C, Sharma A, Chernogubova E, Simeon M . The Role of MicroRNA-21 in Venous Neointimal Hyperplasia: Implications for Targeting miR-21 for VNH Treatment. Mol Ther. 2019; 27(9):1681-1693. PMC: 6731518. DOI: 10.1016/j.ymthe.2019.06.011. View

Li Y, Zhang J, Zhang W, Liu Y, Li Y, Wang K . MicroRNA-192 regulates hypertrophic scar fibrosis by targeting SIP1. J Mol Histol. 2017; 48(5-6):357-366. DOI: 10.1007/s10735-017-9734-3. View

Lin C, Liao Y, Hsieh P, Lu M, Peng C, Chu P . LncRNA GAS5-AS1 inhibits myofibroblasts activities in oral submucous fibrosis. J Formos Med Assoc. 2017; 117(8):727-733. DOI: 10.1016/j.jfma.2017.09.012. View

Yu Y, Sun B, Wang Z, Yang M, Cui Z, Lin S . Exosomes From M2 Macrophage Promote Peritendinous Fibrosis Posterior Tendon Injury via the MiR-15b-5p/FGF-1/7/9 Pathway by Delivery of circRNA-Ep400. Front Cell Dev Biol. 2021; 9:595911. PMC: 8432299. DOI: 10.3389/fcell.2021.595911. View

Zheng S, Hu C, Lin H, Li G, Xia R, Zhang X . circCUL2 induces an inflammatory CAF phenotype in pancreatic ductal adenocarcinoma via the activation of the MyD88-dependent NF-κB signaling pathway. J Exp Clin Cancer Res. 2022; 41(1):71. PMC: 8862589. DOI: 10.1186/s13046-021-02237-6. View

Dong H, Dong S, Zhang L, Gao X, Lv G, Chen W . MicroRNA-214 exerts a Cardio-protective effect by inhibition of fibrosis. Anat Rec (Hoboken). 2016; 299(10):1348-57. DOI: 10.1002/ar.23396. View

Heindryckx F, Binet F, Ponticos M, Rombouts K, Lau J, Kreuger J . Endoplasmic reticulum stress enhances fibrosis through IRE1α-mediated degradation of miR-150 and XBP-1 splicing. EMBO Mol Med. 2016; 8(7):729-44. PMC: 4931288. DOI: 10.15252/emmm.201505925. View

10.

Kuse N, Kamio K, Azuma A, Matsuda K, Inomata M, Usuki J . Exosome-Derived microRNA-22 Ameliorates Pulmonary Fibrosis by Regulating Fibroblast-to-Myofibroblast Differentiation in Vitro and in Vivo. J Nippon Med Sch. 2019; 87(3):118-128. DOI: 10.1272/jnms.JNMS.2020_87-302. View

11.

Cui J, Qi S, Liao R, Su D, Wang Y, Xue S . MiR-574-5p promotes the differentiation of human cardiac fibroblasts via regulating ARID3A. Biochem Biophys Res Commun. 2019; 521(2):427-433. DOI: 10.1016/j.bbrc.2019.09.107. View

12.

Zeng C, Wang Y, Xie C, Sang Y, Li T, Zhang M . Identification of a novel TGF-β-miR-122-fibronectin 1/serum response factor signaling cascade and its implication in hepatic fibrogenesis. Oncotarget. 2015; 6(14):12224-33. PMC: 4494934. DOI: 10.18632/oncotarget.3652. View

13.

Huang C, Wang R, Lu J, He Y, Wu Y, Ma W . MicroRNA-338-3p as a therapeutic target in cardiac fibrosis through FGFR2 suppression. J Clin Lab Anal. 2022; 36(8):e24584. PMC: 9396162. DOI: 10.1002/jcla.24584. View

14.

Liu C, Liao Y, Hsieh P, Yu C, Chueh P, Lin T . miR-1246 as a therapeutic target in oral submucosa fibrosis pathogenesis. J Formos Med Assoc. 2019; 118(7):1093-1098. DOI: 10.1016/j.jfma.2019.02.014. View

15.

Qu C, Liu X, Ye T, Wang L, Liu S, Zhou X . miR‑216a exacerbates TGF‑β‑induced myofibroblast transdifferentiation via PTEN/AKT signaling. Mol Med Rep. 2019; 19(6):5345-5352. PMC: 6522872. DOI: 10.3892/mmr.2019.10200. View

16.

Du W, Xu J, Yang W, Wu N, Li F, Zhou L . A Neuroligin Isoform Translated by circNlgn Contributes to Cardiac Remodeling. Circ Res. 2021; 129(5):568-582. DOI: 10.1161/CIRCRESAHA.120.318364. View

17.

Li N, Wang Z, Gao F, Lei Y, Li Z . Melatonin ameliorates renal fibroblast-myofibroblast transdifferentiation and renal fibrosis through miR-21-5p regulation. J Cell Mol Med. 2020; 24(10):5615-5628. PMC: 7214152. DOI: 10.1111/jcmm.15221. View

18.

Xu C, Hou L, Zhao J, Wang Y, Jiang F, Jiang Q . Exosomal let-7i-5p from three-dimensional cultured human umbilical cord mesenchymal stem cells inhibits fibroblast activation in silicosis through targeting TGFBR1. Ecotoxicol Environ Saf. 2022; 233:113302. DOI: 10.1016/j.ecoenv.2022.113302. View

19.

Savary G, Dewaeles E, Diazzi S, Buscot M, Nottet N, Fassy J . The Long Noncoding RNA DNM3OS Is a Reservoir of FibromiRs with Major Functions in Lung Fibroblast Response to TGF-β and Pulmonary Fibrosis. Am J Respir Crit Care Med. 2019; 200(2):184-198. DOI: 10.1164/rccm.201807-1237OC. View

20.

Huleihel L, Ben-Yehudah A, Milosevic J, Yu G, Pandit K, Sakamoto K . Let-7d microRNA affects mesenchymal phenotypic properties of lung fibroblasts. Am J Physiol Lung Cell Mol Physiol. 2014; 306(6):L534-42. PMC: 3949080. DOI: 10.1152/ajplung.00149.2013. View