MALT1 inhibition by MI‑2 suppresses epithelial‑to‑mesenchymal transition and fibrosis by inactivating the NF‑κB pathway in high glucose‑treated HK‑2 cells

Mucosa‑associated lymphoid tissue lymphoma translocation protein 1 (MALT1) is a scaffold protein and protease that is associated with multiple biological processes, such as immune signaling transduction, inflammation and glucose variation. However, its implication in diabetic nephropathy (DN) is unclear. The present study aimed to investigate the dysregulation of MALT1 and the effect of its inhibition by MI‑2 in high glucose‑treated renal tubular epithelial cells. HK‑2 cells were treated with 15 mM D‑glucose [low‑concentration glucose (LG) group] and 30 mM D‑glucose [high‑concentration glucose (HG)]. The negative control (NC) group consisted of cells cultured only with the standard medium. Subsequently, HK‑2 cells under the HG condition were treated with 0, 1, 2 and 4 µM MI‑2, an inhibitor of MALT1. Cell migration rate, invasive cell count, and the expression levels of vimentin, α‑smooth muscle actin (α‑SMA), fibronectin (FN) and Collagen I were increased, whereas E‑cadherin expression was decreased in the HG group compared with that in the NC group (all P<0.01), implying enhanced epithelial‑to‑mesenchymal transition (EMT) and fibrosis in the HG group. Furthermore, MALT1 was upregulated in the HG group compared with that in the NC group (P<0.01). Following MI‑2 treatment in cells under the HG condition, the inhibitory effects of MI‑2 on EMT, fibrosis and the NF‑κB pathway were dose‑dependent. Cell migration rate, invasive cell count and vimentin expression were reduced, whereas E‑cadherin expression was elevated; furthermore, the expression levels of α‑SMA, FN and Collagen I were downregulated in the high concentration MI‑2 (HC‑MI‑2) group compared with those in the HG group (all P<0.01). In addition, the NF‑κB pathway was inactivated, as reflected by increased inhibitor of κB α expression and decreased phosphorylated-p65 expression in the HC‑MI‑2 group compared with in the HG group (both P<0.001). In conclusion, MALT1 inhibition by MI‑2 suppresses EMT and fibrosis by inactivating the NF‑κB pathway in HG‑treated HK‑2 cells, indicating its potency as a target for DN.

NF‑κB pathway; epithelial‑to‑mesenchymal transition; fibrosis; high glucose‑treated HK‑2 cells; mucosa‑associated lymphoid tissue lymphoma translocation protein 1.