In:
Lab on a Chip, Royal Society of Chemistry (RSC)
Abstract:
Although renal fibrosis can advance chronic kidney disease and progressively lead to end-stage renal failure, no effective anti-fibrotic drugs have been clinically approved. To aid drug development, we developed a biomimetic renal fibrosis progression model on-chip to evaluate anti-fibrotic effects of natural killer cell-derived extracellular vesicles and pirfenidone (PFD) across different fibrotic stages. First, the dynamic interplay between fibroblasts and kidney-derived extracellular matrix (ECM) resembling the fibrogenic niche on-chip demonstrated that myofibroblasts induced by Stiff ECM in 3 days were reversed to fibroblasts by switching to Soft ECM was within 2, but not 7 days. Second, PFD significantly down-regulated the expression of α-SMA in NRK-49F in Medium ECM, as opposed to Stiff ECM. Third, study in rats showed that early administration of PFD significantly inhibited renal fibrosis in terms of the expression level of α-SMA and YAP. Taken together, both on-chip and animal models indicate the importance of early anti-fibrotic intervention for checking the progression of renal fibrosis. Therefore, this renal fibrosis progression on-chip with a feature of recapitulating dynamic biochemical and biophysical cues can be readily used to assess anti-fibrotic candidates and to explore the tipping point when the fibrotic fate can be rescued for better medical intervention.
Type of Medium:
Online Resource
ISSN:
1473-0197
,
1473-0189
Language:
English
Publisher:
Royal Society of Chemistry (RSC)
Publication Date:
2023
detail.hit.zdb_id:
2056646-3
SSG:
12