The Rabep1-Mediated Endocytosis and Activation of Trypsinogen to Promote Pancreatic Stellate Cell Activation

Abstract

Background: The pathogenesis of chronic pancreatitis is still unclear. Trypsinogen activation is an active factor in acute pancreatitis that has not been studied in the occurrence of chronic pancreatitis. Methods: Immunofluorescence was used to detect the location and expression of trypsinogen in chronic pancreatitis and normal tissues. Microarray and single-cell RNA-seq (scRNA-seq) were used to screen core genes and pathways in pancreatic stellate cells (PSCs). Western blotting and immunofluorescence were used to verify trypsinogen expression in PSCs after silencing Rabep1. Immunofluorescence and flow cytometry were used to validate trypsinogen activation and PSC activation after intervening in the endocytosis pathway. Results: Endocytosed trypsinogen was found in PSCs in CP clinical samples. Bioinformatic analysis showed that Rabep1 is a core gene that regulates trypsinogen endocytosis through the endocytosis pathway, verified by Western blot and immunofluorescence. Immunofluorescence and flow cytometry analyses confirmed the activation of trypsinogen and PSCs through the endocytosis pathway in PSCs. Conclusion: This study discovered a new mechanism by which trypsinogen affects the activation of PSCs and the occurrence and development of CP. Through communication between pancreatic acinar cells and PSCs, trypsinogen can be endocytosed by PSCs and activated by the Rabep1 gene.

Identification of JPX-RABEP1 Pair as an Immune-Related Biomarker and Therapeutic Target in Pulmonary Arterial Hypertension by Bioinformatics and Experimental Analyses

“…Many immune-related lncRNA-mRNA pairs were found through co-expression analyses, but only one pair ( JPX-RABEP1 ) was verified by another dataset and experiment, which showed the accuracy as well as importance of this pair. Rabaptin , RAB GTPase binding effector protein 1 ( RABEP1 ) also known as Rbpt5 , is involved in vesicle-mediated transport and located in the endocytic vesicle and endosome [ 33 ]. It is a long-established regulator of early endosome function in targeting the autophagy machinery to early endosomes damaged by chloroquine [ 34 ].…”