Table 3: MicroRNAs Linked to Fibrosis

MicroRNA Effect Organ Predicted Target and Confirmation Level Putative Role in Fibrosis References
let-7d Anti-fibrotic Lung Reporter gene assay (HMGA2) ↓EMT [48]
miR-107 Anti-fibrotic Kidney - ↓ Interstitial fibrosis in allograft transplant [49]
miR-132 Anti-fibrotic Heart, liver Target mRNA changes in mimic/silencing miRNA transfection (RAS-GTPase, MeCP2) ↑angiogenesis and ↓myofibroblasts differentiation [50, 51]
miR-133 Anti-fibrotic Heart Reporter gene assay (CTGF, TGF-β1) ↓ TGF-β signaling and ↓CTGF signaling [52, 53]
miR-141 Anti-fibrotic Kidney Reporter gene assay (TGF-β2) ↓TGF-β and ↓TGF-β dependent EMT [54]
miR-142-3p Pro-fibrotic Kidney - ↓Interstitial fibrosis in allograft transplant [49]
miR-15b, miR-16 Anti-fibrotic Liver, lung Reporter gene assay (Bcl-2) ↑apoptosis [55, 56]
miR-150 Anti-fibrotic Liver Target protein changes in mimic/silencing miRNA transfection (c-myb) ↓activation and proliferation in HSC [57]
miR-155 Pro-fibrotic Lung, liver Reporter gene assay (KGF-FGF-7); target protein changes in mimic/silencing miRNA transfection ↓mesenchymal-epithelial cross-talk [58, 59]
miR-17-92 cluster (miR-18a, 19a/b) Anti-fibrotic Liver, heart, lung Target protein changes in mimic/silencing miRNA transfection (CTGF; CTGF and TSP-1) ↓CTGF and ↓ TSP-1 [48, 60, 61]
miR-192 Pro-fibrotic Kidney Reporter gene assay (ZEB1/2) ↑collagen synthesis and ↑EMT [62, 63]
miR-194 (clustered with miR-215) Anti-fibrotic Liver Target protein changes in mimic/silencing miRNA transfection (rac1) ↓activation and ↓ proliferation in HSC [57]
miR-199a/b Pro-fibrotic Heart, Liver Reporter gene assay (Dyrk1); ↑ECM synthesis via calcineurin/NFAT signaling [64, 65]
miR-200 family (miR-200a/b) Anti-fibrotic Kidney, liver Reporter gene assay (TGFβ2 for miR-200a, ZEB1/2 for miR-200b); target mRNA changes in mimic/silencing miRNA transfection ↓TGF-β signaling and ↓ TGF-β -dependent EMT [54, 59, 66]
miR-204 Anti-fibrotic Kidney - ↓Interstitial fibrosis in allograft transplant [49]
miR-208 Pro-fibrotic Heart Reporter gene assay (THRAP1 and myostatin) ↓myocardial contractility and ↑fibrosis by de-repression of negative regulators of stress-response genes [67]
miR-21 Pro-fibrotic Lung, heart, kidney Reporter gene assay (Smad7 in lung); in vivo functional assay (Spry1 in heart); in vitro functional assay for Smad interactions ↑TGF-β canonical (via Smad7 de-repression of Smad2/3) and non canonical signaling (via Spry1 de-repression of ERK/MAPK) [68-70]
miR-211 Anti-fibrotic Kidney - ↓Interstitial fibrosis in allograft transplant [49]
miR-215 Pro-fibrotic Kidney Reporter gene assay (ZEB1/2) ↑EMT [63]
miR-216, miR-217 Pro-fibrotic Kidney Reporter gene assay (PTEN) ↑Akt signaling via PTEN de-repression [71]
miR-23a (clustered with miR-27a) Pro-fibrotic Lung Systems biology approach and real time PCR (ZEB1) ↑EMT [72]
miR-26a/b Anti-fibrotic Lung Microarray - [48]
miR-27b, miR-27a Pro-fibrotic Liver Reporter gene assay (RXR-α) ↑lipid accumulation and ↑proliferation of HSC [73]
miR-29a/b/c Anti-fibrotic SSc, heart, lung, kidney, liver Reporter gene assays (different collagens, FBN1, ELN1, MMP2, ITGB1; target mRNA changes in mimic/silencing miRNA transfection Directly ↓ECM synthesis [47, 48, 59, 74-77]
miR-30c Anti-fibrotic Heart, lung Reporter gene assay (CTGF) ↓CTGF signaling [48, 51]
miR-32 Pro-fibrotic Kidney - ↓Interstitial fibrosis in allograft transplant [49]
miR-335 Anti-fibrotic Liver Target mRNA changes in mimic/silencing miRNA transfection (TNC) ↓HSC activation and migration [78]
miR-338* Pro-fibrotic Lung Reporter gene assay (LPA1) ↑fibroblast proliferation [79]
miR-34a Pro-fibrotic Liver Reporter gene assay (ACSL1) ↑lipids biosynthesis [59, 80]
miR-377 (clustered with miR-382) Pro-fibrotic Kidney Reporter gene assay (PAK1, SOD) ↑fibronectin synthesis [81]
miR-382 Pro-fibrotic Kidney Reporter gene assay (SOD2) ↑EMT mediated by ↓ protection against mitochondrial oxidative stress [82]
miR-449a/b Anti-fibrotic Kidney Target mRNA changes in mimic/silencing miRNA transfection (SERPINE1) ↑ECM synthesis in hypoxic conditions via downregulation of miR-449 [83]
miR-590 Anti-fibrotic Heart Reporter gene assay (TGFβR2) ↓TGF-β signaling [53]

EMT = epithelial-to-mesenchymal transition; HMGA2 = high mobility group AT-hook 2; RAS-GTPase = Rat sarcoma guanosine triphosphatase; MeCP2 = methylCpG binding protein 2; CTGF = connective tissue growth factor; TGF-β = transforming growth factor- β; Bcl-2 = B-cell lymphoma 2; HSC = hepatic stellate cell; c-myb = avian myeloblastosis proto-oncoprotein; KGF = keratinocytes growth factor; ZEB = zinc finger E-box-binding homebox; rac1 = Ras-related C3 botulinum toxin substrate 1; Dyrk1 = dual-specificity tyrosine-(Y)-phosphorylation regulated kinase 1a; NFAT = nuclear factor of activated T-cells; βMHC = β myosin heavy chain; Smad = small mother against decapentaplegic; Spry1 = protein sprouty homolog 1; ERK = extracellular signal-regulated kinase; MAPK = mitogen activated protein kinase; PTEN = phosphatase and tensin homolog; Akt = non-specific serine/threonine-protein kinase; RXR-α = retinoid X receptor-α; FBN1 = fibrillin1; ELN1 = elastin1; MMP2 = metalloproteinase 2; ITGB1 = integrin β1; TNC = tenascin; LPA1 = lipophosphatidic acid; ACSL1 = Long-chain-fatty-acid-CoA ligase 1; PAK1 = p21 activated kinase 1; SOD = superoxide dismutase; TGF-β receptor 2 = transforming growth factor- β receptor type 2; TSP-1 = thrombospondin-1.