Table 1.
Selected miRNAs associated with fibrotic diseases involving the GIT
| Disease Associations | Deregulated Human miRNAs; Chromosome Location | Deregulation in Disease | Validated miR Targets | Affected Pathways and Final Effect in Disease Due to miR Deregulation | Sites Affected and Complications/Clinical Consequences of Fibrosis in Disease | References |
|---|---|---|---|---|---|---|
| Scleroderma (GIT involvement) | 29a and 29b1; chromosome 7 | Downregulated | Col 1A1, Col 1A2 |
PDGF-β and TGF-β, resulting in increased production of type I and type III collagen | Esophagus: Most common site of GIT involvement in SSc. Leads to GERD, stenosis, strictures, and Barrett's esophagus (due to chronic GERD) | 53, 60, 101, 120, 124, 139 |
| Stomach: Watermelon stomach (gastric antral vascular ectasia) and delayed gastric emptying | ||||||
| 29b2 and 29c; chromosome 1 | Col 3A1, ELN, FBN1 |
Small intestine: pseudo-obstruction, malabsorption syndrome (due to bacterial overgrowth), and PCI, constipation, and diarrhea | ||||
| Colon: Pseudo-obstruction, intestinal perforation, constipation, and diarrhea | ||||||
| 92a; chromosome 13 | Upregulated | Integrin αv | Integrin overexpression leading to activation of TGF-β. This results in increased ECM synthesis. | Rectum and anal canal: 2nd most common site of GIT involvement. Constipation (due to impaired relaxation of fibrotic internal anal sphincter). Fecal incontinence and rectal prolapse | ||
| 150; chromosome 19 | Downregulated | Integrinβ3 | Integrin overexpression leading to activation of TGF-β. This results in increased ECM synthesis. | |||
| 196a; chromosomes 12 and 17 | Downregulated | Col1A1, Col1A2 | TGF-β pathway leading to increased collagen production | |||
| 21; chromosome 17 | Upregulated | Smad7 | TGF-β pathway leading to increased collagen production | |||
| Crohn's disease (GIT fibrosis) | 200b; chromosome 1 | Downregulated | ZEB1 and ZEB2 | EMT resulting in increased ECM production | Esophagogastroduodenum: fistulae>strictures Jejunum: strictures > fistulae Ileum: fistulae>strictures Colon: fistulae>>>strictures Anoperineum: fistulae>>>strictures |
20, 69, 92 |
| 19a-3p; chromosome 13 | Downregulated | CTGF and TSP-1 | ||||
| 19b-3p; chromosome13 | Increased collagen production | |||||
| 29b; chromosomes 1 and 7 | Downregulated | Col 1A1, | PDGF-β and TGF-β, resulting in increased production of type I and type III collagen | |||
| Col 1A2, Col 3A1 |
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ECM, extracellular matrix; ELN, elastin; FBN1, fibrillin; GIT, gastrointestinal tract; GERD, gastroesophageal reflux disease; miR, miRNA; PCI, pneumatosis cystoides intestinalis; SSc, scleroderma; ZSB, zinc finger E-box-binding homeobox.