A micro RNA processing defect in rapidly progressing idiopathic pulmonary fibrosis.

A recent study by Dr. Hogaboam and colleagues reported that loss of microRNA processing components Dicer, AGO1 and AGO2 was found in IPF fibroblasts, even more significant in rapid progressive group.  Here is the medline abstract.

A micro RNA processing defect in rapidly progressing idiopathic pulmonary fibrosis
PLoS One. 2011;6(6):e21253. Epub 2011 Jun 21.
Oak SR, Murray L, Herath A, Sleeman M, Anderson I, Joshi AD, Coelho AL, Flaherty KR, Toews GB, Knight D, Martinez FJ, Hogaboam CM.

Source

Department of Pathology, University of Michigan Medical School, Ann Arbor, Michigan, United States of America.

Abstract

BACKGROUND:

Idiopathic pulmonary fibrosis exhibits differential progression from the time of diagnosis but the molecular basis for varying progression rates is poorly understood. The aim of the present study was to ascertain whether differential miRNA expression might provide one explanation for rapidly versus slowly progressing forms of IPF.

METHODOLOGY AND PRINCIPAL FINDINGS:

miRNA and mRNA were isolated from surgical lung biopsies from IPF patients with a clinically documented rapid or slow course of disease over the first year after diagnosis. A quantitative PCR miRNA array containing 88 of the most abundant miRNA in the human genome was used to profile lung biopsies from 9 patients with rapidly progressing IPF, 6 patients with slowly progressing IPF, and 10 normal lung biopsies. Using this approach, 11 miRNA were significantly increased and 36 were significantly decreased in rapid biopsies compared with normal biopsies. Slowly progressive biopsies exhibited 4 significantly increased miRNA and 36 significantly decreased miRNA compared with normal lung. Among the miRNA present in IPF with validated mRNA targets were those with regulatory effects on epithelial-mesenchymal transition (EMT). Five miRNA (miR-302c, miR-423-5p, miR-210, miR-376c, and miR-185) were significantly increased in rapid compared with slow IPF lung biopsies. Additional analyses of rapid biopsies and fibroblasts grown from the same biopsies revealed that the expression of AGO1 and AGO2 (essential components of the miRNA processing RISC complex) were lower compared with either slow or normal lung biopsies and fibroblasts.

CONCLUSION:

These findings suggest that the development and/or clinical progression of IPF might be the consequence of aberrant miRNA processing.

PMID: 21712985

[PubMed - in process]