CLDN-1 promoted the epithelial to migration and mesenchymal transition (EMT) in human bronchial epithelial cells via Notch pathway

Abstract

Claudin-1 (CLDN-1) is one of main tight junction components that play an important role in epithelial-mesenchymal transition (EMT). However, the effects of CLDN-1 on the migration and EMT induced by TGF-β1 in primary normal human bronchial epithelial (NHBE) and BEAS-2B cells have not been clear. The expression of CLDN-1 was quantified by Western blotting in NHBE and BEAS-2B cells. Cell migration and invasion were detected using transwell assays. The expression level of E-cadherin, N-cadherin, α-SMA, and Vimentin was evaluated by quantitative real-time PCR and Western blotting. Here we showed that the protein expression of CLDN-1 was increased exposed to TGF-β1 in a dose- and time-dependent manner. Knockdown of CLDN-1 using small interfering CLDN-1 RNA (siCLDN-1) prevented the migration and invasion in NHBE and BEAS-2B cells. Moreover, depletion of CLDN-1 promoted the E-cadherin expression and decreased the mRNA and protein levels of N-cadherin, α-SMA, and Vimentin induced by TGF-β1. Furthermore, CLDN-1 silencing resulted in the reduction of the Notch intracellular domain (NICD) and hairy enhancer of split-1 (Hes-1) in mRNA and protein level. Jagged-1, an activator of Notch signaling pathway, abrogated the protective function of siCLDN-1 in migration and EMT. In conclusion, CLDN-1 promoted the migration and EMT through the Notch signaling pathway.

Small molecule inhibitors of epithelial‐mesenchymal transition for the treatment of cancer and fibrosis

“…Extensive studies have demonstrated that the Notch signaling pathway is also critical for EMT in tumorigenesis and fibrogenesis. The overexpression of Notch1‐induced EMT in PC‐3 cells, and claudin‐1 contributed to EMT by the Notch signaling pathway in human bronchial epithelial cells . In addition, Notch and TGF‐β1 generated a reciprocal positive regulatory loop and cooperatively regulated EMT in epithelial ovarian cancer cells, which provided new insight into the mechanism of EMT .…”

“…The overexpression of Notch1-induced EMT in PC-3 cells, and claudin-1 contributed to EMT by the Notch signaling pathway in human bronchial epithelial cells. 180,181 In addition, Notch and TGF-β1 generated a reciprocal positive regulatory loop and cooperatively regulated EMT in epithelial ovarian cancer cells, which provided new insight into the mechanism of EMT. 182 Moreover, miR-34a downregulation induced by hypoxia enhanced EMT via the Notch signaling pathway in tubular epithelial cells, which indicated that the Notch signaling pathway is critical for EMT during fibrosis.…”

Urine single cell RNA-sequencing in focal segmental glomerulosclerosis reveals inflammatory signatures in immune cells and podocytes

“…S3) and it is possible to assume that there were some PECs in the podocyte cluster. However, PECs are also known to undergo EMT and these markers are also reported to be involved in the EMT process 29,30,31,32,33 and are also highly expressed in tubular and collecting ductal cell clusters, making it challenging to confirm their presence in the current study.…”

lncRNA MIAT increases cell viability, migration, EMT and ECM production in age‑related cataracts by regulating the miR‑181a/CTGF/ERK signaling pathway

“…2B and C ). α-SMA is a marker of EMT ( 26 ), and FN and COL-1 are ECM markers ( 27 ). Therefore, the effect of MIAT knockdown on the protein expression levels of α-SMA, FN and COL-1 was investigated.…”

“…Accumulating evidence has suggested that the ERK signaling pathway is associated with the development of multiple diseases ( 26 ). For example, one study reported that ERK signaling was activated during the development of Kashin-Beck disease ( 37 ).…”