Home > Browse Issues > Vol.37 No.1
Dialogue between TGF-β1 and Hedgehog-Gli1 Signaling Regulates Phenotypic Changes of Renal Tubular Epithelial Cells and Collagen Deposition
Liang Yong1, Lu Hong2, Lin Chengcheng1, Wang Silu1, Xia Peng3, Wu Cunzao3, Chen Bicheng1, Bai Yongheng1*
1Surgery Laboratory, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, China;2Department of Laboratory Medicine, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, China;3Department of Transplantation, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, China
Abstract: The aim of this study was to investigate effect of Hedgehog-Gli1 (HH) signaling in phenotypic changes of renal tubular epithelial cells and its association with TGF-β1. Rat renal tubular epithelial cells (NRK-52E) were treated with 1~50 ng/mL of exogenous recombinant sonic hedgehog (Shh)， or 5 ng/mL of TGF-β1， or HH signaling inhibitor cyclopamine (5 μmol/L) for 24 hours. qRT-PCR， immunofluorescence staining and Western blot were performed to detect mRNA or protein expressions of HH signaling-related molecules (Ptch1， Smo and Gli1)， TGF-β1， EMT markers (α-SMA， E-cadherin and Rac1) and type III collagen. The levels of TGF-β1 were detected by ELISA assay. Our results showed that Shh increased the expression of Smo and Gli1 and decreased the expression of Ptch1， suggesting that HH signaling was activated. Activated HH signaling resulted in down-regulated expression of E-cadherin and up-regulated expression of α-SMA and type III collagen. In Shh-treated NRK-52E cells， the levels of TGF-β1 were also enhanced， but inhibited by cyclopamine. Cyclopamine also inhibited EMT and ECM deposition. In cultured NRK-52E cells， recombinant TGF-β1 not only induced EMT， but also increased the activity of HH signaling. Thus， these findings suggested that both HH signaling and TGF-β1 were involved in EMT and ECM accumulation in vitro. Activation of HH signaling can promote TGF-β1 expression， and TGF-β1 also can activate HH signaling， suggesting that cross-talk between HH signaling and TGF-β1 regulates renal EMT and ECM deposition.
CN
EN