| First Author | Karhadkar TR | Year | 2020 |
| Journal | Am J Physiol Lung Cell Mol Physiol | Volume | 318 |
| Issue | 1 | Pages | L165-L179 |
| PubMed ID | 31617733 | Mgi Jnum | J:282956 |
| Mgi Id | MGI:6384367 | Doi | 10.1152/ajplung.00275.2019 |
| Citation | Karhadkar TR, et al. (2020) Attenuated pulmonary fibrosis in sialidase-3 knockout (Neu3(-/-)) mice. Am J Physiol Lung Cell Mol Physiol 318(1):L165-L179 |
| abstractText | Pulmonary fibrosis involves the formation of inappropriate scar tissue in the lungs, but what drives fibrosis is unclear. Sialidases (also called neuraminidases) cleave terminal sialic acids from glycoconjugates. In humans and mice, pulmonary fibrosis is associated with desialylation of glycoconjugates and upregulation of sialidases. Of the four mammalian sialidases, we previously detected only NEU3 in the bronchoalveolar lavage fluid from mice with bleomycin-induced pulmonary fibrosis. In this report, we show that NEU3 upregulates extracellular accumulation of the profibrotic cytokines IL-6 and IL-1beta, and IL-6 upregulates NEU3 in human peripheral blood mononuclear cells, suggesting that NEU3 may be part of a positive feedback loop potentiating fibrosis. To further elucidate the role of NEU3 in fibrosis, we used bleomycin to induce lung fibrosis in wild-type C57BL/6 and Neu3(-/-) mice. At 21 days after bleomycin, compared with male and female C57BL/6 mice, male and female Neu3(-/-) mice had significantly less inflammation, less upregulation of other sialidases and the profibrotic cytokine active transforming growth factor beta1, and less fibrosis in the lungs. Our results suggest that NEU3 participates in fibrosis and that NEU3 could be a target to develop treatments for fibrosis. |
