RNA-seq implicates deregulation of the immune system in the pathogenesis of diverticulitis.

American journal of physiology. Gastrointestinal and liver physiology

PubMedID: 28619727

Schieffer KM, Choi CS, Emrich S, Harris L, Deiling S, Karamchandani DM, Salzberg A, Kawasawa YI, Yochum GS, Koltun WA. RNA-seq implicates deregulation of the immune system in the pathogenesis of diverticulitis. Am J Physiol Gastrointest Liver Physiol. 2017;ajpgi.00136.2017.
Individuals with diverticula or outpouchings of the colonic mucosa and submucosa through the colonic wall have diverticulosis, which is usually asymptomatic. In 10-25% of individuals, the diverticula become inflamed, resulting in diverticulitis. Very little is known about the pathophysiology or gene regulatory pathways involved in the development of diverticulitis. To identify these pathways, we deep sequenced RNAs isolated from full-thickness sections of sigmoid colon from diverticulitis patients and control individuals. Specifically for diverticulitis cases, we analyzed tissue adjacent to areas affected by chronic disease. Since the tissue was collected during elective sigmoid resection, the disease was in a quiescent state. A comparison of differentially expressed genes found that Gene Ontology (GO) pathways associated with the immune response were up-regulated in diverticulitis patients compared to non-diverticulosis controls. Next, weighted gene co-expression network analysis was performed to identify the interaction between co-expressed genes. This analysis revealed RASAL3, SASH3, PTPRC, and INPP5D as hub genes within the brown module eigengene, which highly correlated (r=0. 67, P=0. 0004) with diverticulitis. Additionally, we identified elevated expression of downstream interacting genes. In summary, transcripts associated with the immune response were up-regulated in adjacent tissue from the sigmoid colons of chronic, recurrent diverticulitis patients. Further elucidating the genetic or epigenetic mechanisms associated with these alterations can help identify those at-risk for chronic disease and may assist in clinical decision management.