EGF receptor-dependent mechanism may be involved in the Tamm-Horsfall glycoprotein-enhanced PMN phagocytosis via activating Rho family and MAPK signaling pathway

KO-JEN LISiao, Sue-CienSue-CienSiaoCHENG-HAN WUCHIEH-YU SHENWu, Tsai-HungTsai-HungWuTsai, Chang-YouhChang-YouhTsaiSONG-CHOU HSIEHCHIA-LI YU2022-02-102022-02-102014-01-211420-3049https://scholars.lib.ntu.edu.tw/handle/123456789/593968Our previous studies showed that urinary Tamm-Horsfall glycoprotein (THP) potently enhanced polymorphonuclear neutrophil (PMN) phagocytosis. However, the domain structure(s), signaling pathway and the intracellular events responsible for THP-enhanced PMN phagocytosis remain to be elucidated. THP was purified from normal human urine. The human promyelocytic leukemia cell line HL-60 was induced to differentiate into PMNs by all-trans retinoid acid. Pretreatment with different MAPK and PI3K inhibitors was used to delineate signaling pathways in THP-enhanced PMN phagocytosis. Phosphorylation of molecules responsible for PMN phagocytosis induced by bacterial lipopolysaccharide (LPS), THP, or human recombinant epidermal growth factor (EGF) was evaluated by western blot. A p38 MAPK inhibitor, SB203580, effectively inhibited both spontaneous and LPS- and THP-induced PMN phagocytosis. Both THP and LPS enhanced the expression of the Rho family proteins Cdc42 and Rac that may lead to F-actin re-arrangement. Further studies suggested that THP and EGF enhance PMN and differentiated HL-60 cell phagocytosis in a similar pattern. Furthermore, the EGF receptor inhibitor GW2974 significantly suppressed THP- and EGF-enhanced PMN phagocytosis and p38 and ERK1/2 phosphorylation in differentiated HL-60 cells. We conclude that EGF receptor-dependent signaling may be involved in THP-enhanced PMN phagocytosis by activating Rho family and MAP kinase.enTamm-Horsfall glycoprotein; phagocytosis; EGF-like domains; Rho family; MAP kinase; JUVENILE HYPERURICAEMIC NEPHROPATHY; FACTOR-LIKE DOMAIN; MEDIATED PHAGOCYTOSIS; URINARY GLYCOPROTEIN; HUMAN NEUTROPHILS; PROTEIN BINDS; UROMODULIN; CDC42; GLYCOSYLATION; EXPRESSIONEGF receptor-dependent mechanism may be involved in the Tamm-Horsfall glycoprotein-enhanced PMN phagocytosis via activating Rho family and MAPK signaling pathwayjournal article10.3390/molecules19011328244512522-s2.0-84893031183WOS:000334420300085https://scholars.lib.ntu.edu.tw/handle/123456789/540826