Synthetic peptides derived from the Schistosoma mansoni secretory protein Sm16 induce contrasting responses in hepatic stellate cells

• Published in: Experimental parasitology Vol. 236-237; p. 108255
• Main Authors: Carson, Jack P., Robinson, Mark W., Ramm, Grant A., Gobert, Geoffrey N.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.05.2022
• Subjects: Fibrosis; Hepatic stellate cell; LX-2; Schistosoma mansoni; Sm16; Sm16; Schistosoma mansoni; LX-2; Hepatic stellate cell; Fibrosis
• ISSN: 0014-4894; 1090-2449
• DOI: 10.1016/j.exppara.2022.108255

Sm16 is a 16 KDa protein released by Schistosoma mansoni that modulates inflammatory responses in host cells. Sm16 is expressed by several life cycle stages of S. mansoni, including the egg stage. Schistosome eggs are known to provoke chronic schistosomiasis pathology, which involves the development of liver fibrosis. Hepatic stellate cells (HSCs), which are responsible for this fibrosis, are susceptible to immunomodulation by S. mansoni whole egg secretions. To define the effects of Sm16 exposure on HSCs, two synthetic peptide derivatives of Sm16, coined “KS-84″ and “KS-66″, were tested against LX-2 cells, an immortalised human HSC line, and RNA sequencing was used to assess the transcriptional changes induced by each peptide. In total, 78 and 798 genes were found to be significantly differentially expressed by KS-84 and KS-66 treatment, respectively. In silico pathway analysis of these genes revealed that KS-84 reduced LX-2 cell activation and fibrotic potential, whereas KS-66 increased both processes. Reduced transforming growth factor-β1 (TGF-β1) signalling was identified as a potential mechanism of KS-84-induced inhibition of LX-2 activation. Taken together, these findings indicate a potential role for Sm16 in combatting fibrotic liver disease. [Display omitted] •Peptide derivatives of the S. mansoni protein Sm16 alter the responses of HSCs.•KS-84 was predicted to inhibit HSC activation and fibrotic potential.•Reduced TGF-β signaling was identified as a possible mechanism for this inhibition.•Sm16-derived peptides may have a role in combatting fibrotic liver disease.