Inhibiting Sialidase-Induced TGF-β1 Activation Attenuates Pulmonary Fibrosis in Mice.

ABSTRACT: The active form of transforming growth factor-β1 (TGF-β1) plays a key role in potentiating fibrosis. TGF-β1 is sequestered in an inactive state by a latency-associated glycopeptide (LAP). Sialidases (also called neuraminidases (NEU)) cleave terminal sialic acids from glycoconjugates. The sialidase NEU3 is upregulated in fibrosis, and mice lacking Neu3 show attenuated bleomycin-induced increases in active TGF-β1 in the lungs and attenuated pulmonary fibrosis. Here we observe that recombinant human NEU3 upregulates active human TGF-β1 by releasing active TGF-β1 from its latent inactive form by desialylating LAP. Based on the proposed mechanism of action of NEU3, we hypothesized that compounds with a ring structure resembling picolinic acid might be t

SUBMITTER: Karhadkar TR 

PROVIDER: S-EPMC7788355 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature