Synthetic TGF-β1/Smad Oligodeoxynucleotide Attenuated Renal Fibrosis via Regulation of both Epithelial and Endothelial Mesenchymal Transition (EMT/Endomt) in Unilateral Ureteral Obstruction
Mi-Gyeong Gwon, MS; Hyun-Jin An, PhD; Jung-Yeon Kim, PhD; HyeMin Gu, BS; Kwan-Kyu Park, MD
Catholic University of Daegu, Daegu, Korea, Republic of
Background: Kidney interstitial fibrosis is common process of kidney disease leading to end-stage of renal failure irrespective of etiology. Excessive accumulation of extracellular matrix (ECM) produced by myofibroblasts is an important characteristic in kidney fibrosis. Recent studies have demonstrated that epithelial and endothelial cells become myofibroblasts by epithelial-mesenchymal transition (EMT) and endothelial-mesenchymal transition (EndoMT). TGF-β1/Smad signaling plays a crucial role in EMT and EndoMT. TGF-β1/Smad oligodeoxynucleotide (ODN) is a synthetic short DNA containing complementary sequence for Smad transcription factor and TGF-β1 mRNA. This study investigated whether both EMT and EndoMT processes are involved in kidney fibrosis and to examine the anti-fibrotic effect of synthetic TGF-β1/Smad ODN on kidney fibrosis via regulation of both EMT and EndoMT. Methods: To examine the anti-fibrotic effect of synthetic TGF-β1/Smad ODN, we performed histological staining, western blotting and immunofluorescence to evaluate renal interstitial fibrosis. Results: The results showed that UUO induced accumulation of collagen and raised kidney tubular atrophy. However, synthetic ODN for TGF-β1/Smad significantly suppressed UUO-induced fibrosis via attenuated EMT and EndoMT processes. As shown Western blot and immunofluorescence data, the epithelial and endothelial markers were recovered in TGF-β1/Smad ODN-treated mice compared with UUO mice. In addition, the expressions of mesenchymal markers such as α-SMA and FSP-1 were reduced in ODN-treated mice compare with UUO mice. Conclusions: These results demonstrated that administration of synthetic TGF-β1/Smad ODN attenuates kidney fibrosis via inhibiting both EMT and EndoMT processes. This research proposes the possibility of synthetic ODN as a new effective therapeutic tool for kidney fibrosis.
Keywords: Kidney fibrosis, TGF-β1/Smad oligodeoxynucleotide, EMT, EndoMT, UUO
Back to 2018 Program