MicroRNA (
miRNA) are
small non-coding RNA molecules that posttranscriptionally effect mRNA stability and translation by targeting the 3'-untranslated region (3'-UTR) of various transcripts. Thus, dysregulation of
miRNA affects a wide range of cellular processes such as cell proliferation and differentiation involved in organ remodeling processes. Divergent
miRNA patterns were observed during chronic
liver diseases of various etiologies. Chronic
liver diseases result in uncontrolled
scar formation ending up in
liver fibrosis or even
cirrhosis. Since it has been shown that miR-29 dysregulation is involved in synthesis of
extracellular matrix proteins, miR-29 is of special interest. The importance of miR-29 in hepatic
collagen homeostasis is underlined by in vivo data showing that experimental severe
fibrosis is associated with a prominent miR-29 decrease. The loss of miR-29 is due to the response of hepatic stellate cells to exposure to the profibrogenic mediators TGF-β and
PDGF-BB. Several putative binding sites for the
Smad proteins and the Ap1 complex are located in the miR-29 promoter, which are suggested to mediate miR-29 decrease in
fibrosis. Other
miRNA are highly increased after profibrogenic stimulation, such as miR-21. miR-21 is transcriptionally upregulated in response to Smad-3 rather than Smad-2 activation after TGF-β stimulation. In addition, TGF-β promotes miR-21 expression by formation of a microprocessor complex containing
Smad proteins. Elevated miR-21 may then act as a profibrogenic
miRNA by its repression of the TGF-β inhibitory Smad-7
protein.