Genomics of Human Fibrotic Diseases: Disordered Wound Healing Response.
Rivka C StoneVivien ChenJamie BurgessSukhmani PannuMarjana Tomic-CanicPublished in: International journal of molecular sciences (2020)
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 functional quality of life for patients and decrease mortality from fibrotic diseases.
Keyphrases
- systemic sclerosis
- idiopathic pulmonary fibrosis
- copy number
- wound healing
- case control
- dna methylation
- extracellular matrix
- interstitial lung disease
- single cell
- genome wide
- gene expression
- ejection fraction
- endothelial cells
- end stage renal disease
- liver failure
- oxidative stress
- small molecule
- type diabetes
- cardiovascular disease
- squamous cell carcinoma
- lymph node
- risk factors
- rheumatoid arthritis
- newly diagnosed
- genome wide association
- transcription factor
- hepatitis b virus
- atrial fibrillation
- neoadjuvant chemotherapy
- peritoneal dialysis
- intensive care unit
- drug delivery
- anti inflammatory
- soft tissue
- circulating tumor