Professor CAROL POLLOCK1, WENYANG SHI1, Dr XINMING CHEN1, Dr QINHUA CAO1
1Kolling Institute-renal Research Group, , Australia
Biography:
Bio to come
Background:
Chronic kidney disease (CKD) affects over 850 million people globally, with renal fibrosis being the key driver of progression to end-stage kidney disease. Engrailed-1 (EN-1), a transcription factor involved in fibrotic skin disorders, has recently been implicated in renal fibrosis. This study investigates whether silencing EN-1 in renal fibroblasts can reduce fibrotic activation and collagen production.
Aims:
To assess the therapeutic potential of EN-1 inhibition using siRNA in renal fibroblast activation and compare it with Verteporfin (VP), a known inhibitor of the TGF-β/Smad pathway.
Methods:
An in-vitro model using NRK-49F renal fibroblasts was developed. Cells were stimulated with TGF-β to induce myofibroblast transdifferentiation, and treated with EN-1 siRNA or VP. EN-1, α-SMA, COL1, and FOXM1 protein levels were quantified via Western blot. In vivo EN-1 expression was examined using immunohistochemistry in folic acid- and UUO-induced mouse kidney fibrosis models.
Results:
EN-1 expression was elevated in fibrotic renal tissue and TGF-β-treated fibroblasts. EN-1 silencing significantly reduced α-SMA expression, preserving fibroblast morphology. VP also reduced α-SMA and EN-1 expression in a dose-dependent manner. Collagen-1 levels decreased with both treatments, though not significantly. FOXM1, a marker of Wnt/β-catenin signalling, was downregulated by VP but not by EN-1 siRNA.
Conclusion:
EN-1 is a TGF-β-responsive factor essential for myofibroblast activation. Its inhibition suppresses the fibroblast-to-myofibroblast transition, presenting a novel therapeutic strategy for renal fibrosis. Compared to VP, EN-1 siRNA offers a potentially more specific and less cytotoxic alternative.
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