Uterine leiomyomata and keloids fibrosis origins: a mini-review of fibroproliferative diseases

Abstract

Diseases such as uterine leiomyomata (fibroids and benign tumors of the uterus) and keloids (raised scars) may share common etiology. Fibroids and keloids can co-occur in individuals, and both are highly heritable, suggesting they may share common genetic risk factors. Fibroproliferative diseases are common and characterized by scarring and overgrowth of connective tissue, impacting multiple organ systems. These conditions both have racial disparities in prevalence, with the highest prevalence observed among individuals of African ancestry. Several fibroproliferative diseases are more severe and common in populations of sub-Saharan Africa. This mini-review aims to provide a broad overview of the current knowledge of the evolutionary origins and causes of fibroproliferative diseases. We also discuss current hypotheses proposing that the increased prevalence of these diseases in African-derived populations is due to the selection for profibrotic alleles that are protective against helminth infections and provide examples from knowledge of uterine fibroid and keloid research.

Keywords: benign growth; disparities; fibroproliferative; fibrosis; gynecologic.

Graphical abstract

Figure 1.

Overview of hypothesized role of natural selection in fibrosis. In the absence of helminth, the inflammatory response leads to increased inflammation and prolonged fibrosis by: 1) inhalation of allergens trigger airway allergic immune responses; 2) dendritic cells sample allergens and display pieces of the allergen on their surface on Major Histocompatibility Complex Class II (MHCII); 3) dendritic cells migrate to the lymph node activating T cells and inducing clonal expansion and Th2 polarization; 4) Th2 cells produce type 2 inflammatory cytokines that induce inflammation and fibrosis; 5) a buildup of extracellular matrix could lead to the development of fibroproliferative diseases such as fibroid and keloids. Th2, T-helper cell type-2. This figure was created with Biorender.com.