Genetic susceptibility to interstitial pulmonary fibrosis in mice induced by vanadium pentoxide (V₂O₅)

Abstract

Interstitial lung diseases (ILDs) are characterized by injury, inflammation, and scarring of alveoli, leading to impaired function. The etiology of idiopathic forms of ILD is not understood, making them particularly difficult to study due to the lack of appropriate animal models. Consequently, few effective therapies have emerged. We developed an inbred mouse model of ILD using vanadium pentoxide (V2O5), the most common form of a transition metal found in cigarette smoke, fuel ash, mineral ores, and steel alloys. Pulmonary responses to V2O5, including dose-dependent increases in lung permeability, inflammation, collagen content, and dysfunction, were significantly greater in DBA/2J mice compared to C57BL/6J mice. Inflammatory and fibrotic responses persisted for 4 mo in DBA/2J mice, while limited responses in C57BL/6J mice resolved. We investigated the genetic basis for differential responses through genetic mapping of V2O5-induced lung collagen content in BXD recombinant inbred (RI) strains and identified significant linkage on chromosome 4 with candidate genes that associate with V2O5-induced collagen content across the RI strains. Results suggest that V2O5 may induce pulmonary fibrosis through mechanisms distinct from those in other models of pulmonary fibrosis. These findings should further advance our understanding of mechanisms involved in ILD and thereby aid in identification of new therapeutic targets.

Mechanisms of carbon nanotube‐induced pulmonary fibrosis: a physicochemical characteristic perspective

“…Specifically, the C57BL/6 strain responds greater than DBA/2, Swiss, and BALB/c mice, and the least response was observed from BALB/c mice 108 . Another study examining the fibrotic outcome of pulmonary exposure to vanadium pentoxide in two mouse strains found increased inflammatory and collagen content in DBA/2J mice compared to C57BL/6J mice 109 . Therefore, strain susceptibility to pulmonary fibrosis may depend on the agent used to induce fibrosis.…”

Sex-based differences in lymphocyte proliferation in the spleen after vanadium inhalation

“…Vanadium (V) is adsorbed into PM and by inhalation reaches the systemic circulation exerting its toxic effect in other organs and tissues (Dockery & Pope 1994;Barceloux 1999). Adverse effects by V exposure in reproductive, nervous, urinary, respiratory and hematopoietic systems have been reported (Aragon et al 2005;Gonzalez-Villalva et al 2009;Fortoul et al 2011Fortoul et al , 2014aRodriguez-Lara et al 2013b;Walters et al 2014). Nevertheless, the effects of V on the immune system are not very well studied and many of the reported results have often been contradictory.…”

Metal-Induced Pulmonary Fibrosis

“…These data suggest that several genes are involved in airway remodeling after exposure to V 2 O 5 . When assessing genetic susceptibility to IPF in mice induced by vanadium pentoxide (V 2 O 5 ), pulmonary responses to V 2 O 5 were significantly greater in DBA/2J mice compared to C57BL/6J mice [95]. There were significant dose-dependent increases in lung permeability, inflammation, collagen content and dysfunction.…”