Table 1 The summaries of representative circRNAs in different organ fibrosis

Heart

Doxorubicin-

induced CF

CircNlgn

Upregulated in myocardial tissues of patients with selected congenital heart defects with cardiac overload.

Transgenic mice overexpressing circNlgn impaired cardiac function and induced CF. Silencing circNlgn decreased the effects of doxorubicin on cardiac cell activities and retarded fibrosis.

CircNlgn-derived peptide Nlgn173 could bind and activate H2AX, producing γH2AX, resulting in upregulation of IL-1b, IL-2Rb, IL-6 and EGR1/3.

[45]

Heart

CF

CircYap

Decreased in patients with cardiac hypertrophy and TAC mice.

Ectopic circYap improved heart function and alleviated fibrosis.

CircYap facilitated the binding of TPM4 with ACTG, resulting in increased inhibitory effect of TPM4 on actin polymerization.

[49]

Heart

Myocardial fibrosis

CircUbe3a

Elevated in M2M-SEV in heart of acute myocardial injury.

Impaired cardiac function and exacerbated cardiac fibrosis by promoting the proliferation, migration and differentiation.

Targeting miR-138-5p/RhoC signaling pathway.

[52]

Heart

Cardiac hepatopathy

Circslc8a1

Decreased in mice TAC heart.

Silencing circslc8a1induces cardiac hypertrophy, fibrosis, and hepatic steatosis, and over-expressing it exerts protective effects.

Interacted with mitochondrial-associated proteins, i.e. ATBP, COX5B, NUDFS2, and facilitate ATP production.

[53]

Liver

Radiation-induced liver disease

CircRSF1

Upregulated in irradiated LX2 cells

Promoted the survival and inflammatory as well as fibrotic phenotype of irradiated LX2 cells.

MiR-146a-5p/RAC1

[57]

Liver

CCl4-induced HF

CircFBXW4

Decreased in HF

Overexpression of circFBXW4 inhibited HSC proliferation and activation, induced HSC apoptosis, thereby antagonizing fibrosis.

MiR-18b-3p/FBXW7

[59]

Liver

CCl4-induced HF

CircPSD3

Down-regulated in HF

Inhibited the proliferation and activation of HSC. In vivo overexpression of circPSD3 alleviated hepatic fibrosis.

MiR-92b-3p/smad7

[60]

Liver

CCl4-induced HF

CircUbe2k

Elevated in HF.

Enhanced the activation and and prolifereation of HSC in vivo and in vitro.

MiR-149-5p/TGF-β2

[65]

Liver

NASH

CircSCAR

Decreased in HSC from NASH patients.

Inhibits mitochondrial ROS output and fibroblast activation.

Binds to ATP5B and shut down mPTP by blocking CypD-mPTP interaction.

[69]

Lung

IPF

CircANKRD42

Upregulated in peripheral blood of IPF patients.

Enhanced the mechanical stiffness. Promoted the fibroblasts differentiation, activation and migration, and ECM synthesis.

Directly targets AJUBA and YAP1, through sponging miR-324-5p and miR-136-5p, respectively, and promoted the nuclear translocation of pYAP1, therefore facilitating the transcription of genes related to mechanical stiffness.

[71]

Lung

IPF

CircTADA2A

Downregulated in IPF fibroblasts.

CircTADA2A decreased fibrogenic responses in vivo and vitro.

Targeting miR-526b/Cav1 and miR-203/Cav2 axes

[72]

Lung

Bleomycin-

induced PF

CircHIPK3

Upregulated in pulmonary fibrosis.

Silencing circHIPK3 inhibited fibroblast-to-myofibroblast

transition and suppressed fibroblasts proliferation.

Targeting miR-338-3p/COL1A1, SOX4, or enhancing glycolysis through miR-30a-3p/FOXK axis.

[75]

Renal

FAN

CircHIPK3

Increased in FAN

Promoted the production of profibrotic factors.

Targeting miR-30a and uprelagulating the downstream genes, including FN, TGFb1, COL1.

[81]

Renal

IRI or toxic kidney diseases

CircBNC2

Decreased in IRI or toxic kidney injuries

Ectopic circBNC2 mitigated maladaptive fibrotic repair after kidney injury by improving TEC G2/M arrest.

Translating into a 681-amino-acid protein and promoted CDK1/cyclin B1 complex formation and nuclear translocation, and alleviated TEC G2/M arrest.

[84]

Renal

IRI, UUO and patients with CKD

CircPTPN14

Increased in RF.

Silencing circPTPN14 alleviated the progression of fbrosis in kidneys subjected to IRI or UUO.

Promoting FUSP1 binding to FUSE, which enhances MYC and related fibrotic genes transcription.

[85]

Skin

Keloid tissues and keloid fibroblasts

Circ_0057452

Upregulated in keloid fibroblasts

Knockdown of circ_0057452 inhibited the proliferation, migration, invasion, and collagen synthesis and induced cell cycle arrest and apoptosis of KFs.

MiR-7-5p/GAB1

[89]

Skin

Keloid tissues and keloid fibroblasts

CircCOL5A1

Upregulated in keloid fibroblasts

CircCOL5A1 knockdown repressed the proliferation, migration, ECM deposition and promoted cell apoptosis.

MiR-7-5p/Epac1

[91]