The role of miR-29 in pulmonary fibrosis

Abstract

Pulmonary fibrosis is a pathological condition in which lungs become scarred due to the excess extracellular matrix (ECM) deposition and structural alterations in the interstitium of lung parenchyma. Many patients with interstitial lung diseases (ILDs) caused by long-term exposure to toxic substances, chronic infections, or autoimmune responses develop fibrosis. Etiologies for many ILDs are unknown, such as idiopathic pulmonary fibrosis (IPF), a devastating, relentless form of pulmonary fibrosis with a median survival of 2-3 years. Despite several decades of research, factors that initiate and sustain the fibrotic response in lungs remain unclear and there is no effective treatment to block progression of fibrosis. Here we summarize recent findings on the antifibrotic activity of miR-29, a small noncoding regulatory RNA, in the pathogenesis of fibrosis by regulating ECM production and deposition, and epithelial-mesenchymal transition (EMT). We also describe interactions of miR-29 with multiple profibrotic and inflammatory pathways. Finally, we review the antifibrotic activity of miR-29 in animal models of fibrosis and highlight miR-29 as a promising therapeutic reagent or target for the treatment of pulmonary fibrosis.

Role of the microRNA-29 family in fibrotic skin diseases

“…Various studies have independently demonstrated that the miR-29 family targets >20 ECM-associated genes, including collagen, elastin and integrin B1; therefore, the miR-29 family is a major target of this miRNA family (22,24). miR-29 family members are actively involved in the fibrotic processes of various types of tissue, such as liver (25,36,37), pulmonary (19,38,39), cardiac (40,41) and renal (24,42), as well as in systemic sclerosis (23,(43)(44)(45), trabecular meshwork (9) and bone remodelling (20,21,46). Downregulation of different miR-29 family members has been reported in the liver (25,37,47,48), lungs (19,49), heart (25,41), kidneys (50,51) and skin (23) (Fig.…”

The MicroRNA 29 Family Promotes Type II Cell Differentiation in Developing Lung

“…Members of the miR-29 family are known to target collagens, integrins, basement membrane, and extracellular matrix-remodeling proteins, as well as stem cell factor KLF4 (24,42,43), suggesting that miR-29 family members may mediate reprogramming of cells toward a differentiated epithelial phenotype. Moreover, targeted deletion of miR-29 family members in vivo leads to an immature lung vascular smooth muscle cell phenotype, specifically associated with the distal lung, suggesting their role in lung vascular smooth muscle cell differentiation (44).…”

RNAs that make a heart beat

“…Van Rooij and colleagues found that microRNAs are up-and down-regulated in cardiac tissue from mice undergoing cardiac stress (31), and in response to myocardial infarction (32). Downregulation of miR-29, a microRNA that targets extracellular matrix proteins (33)(34)(35), was found to contribute to the fibrotic response post myocardial infarction (32). Ikeda and colleagues extended these studies to humans, and reported reproducible changes in miRNA levels in human patients with heart failure (36).…”