Genomics of Human Fibrotic Diseases: Disordered Wound Healing Response.

International Journal of Molecular Sciences
Rivka C StoneMarjana Tomic-Canic

Abstract

Fibrotic disease, which is implicated in almost half of all deaths worldwide, is the result of an uncontrolled wound healing response to injury in which tissue is replaced by deposition of excess extracellular matrix, leading to fibrosis and loss of organ function. A plethora of genome-wide association studies, microarrays, exome sequencing studies, DNA methylation arrays, next-generation sequencing, and profiling of noncoding RNAs have been performed in patient-derived fibrotic tissue, with the shared goal of utilizing genomics to identify the transcriptional networks and biological pathways underlying the development of fibrotic diseases. In this review, we discuss fibrosing disorders of the skin, liver, kidney, lung, and heart, systematically (1) characterizing the initial acute injury that drives unresolved inflammation, (2) identifying genomic studies that have defined the pathologic gene changes leading to excess matrix deposition and fibrogenesis, and (3) summarizing therapies targeting pro-fibrotic genes and networks identified in the genomic studies. Ultimately, successful bench-to-bedside translation of observations from genomic studies will result in the development of novel anti-fibrotic therapeutics that improve fu...Continue Reading

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Citations

Mar 11, 2021·Experimental Dermatology·Irena PastarMarjana Tomic-Canic

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Methods Mentioned

BETA
RNA-seq
biopsy
methylation profiling
genotyping
biopsies

Software Mentioned

eMERGE

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