The expression of RIPK3 is associated with cell turnover of gastric mucosa in the mouse and human stomach

Guanglin Cui,Yanan Wang,Zhenfeng Li,Yaobo Yuan

doi:10.1007/s10735-021-10001-5

Abstract

Necroptosis is a novel manner of programmed cell death and important for tissue development, homeostasis, damage, and repair. Activation of receptor-interacting protein kinase 3 (RIPK3), a key member of receptor-interacting protein family in contributing significantly to necroptosis, in tissues is a hallmark of cells dying by necroptosis. However, there are few studies that examine the expression of RIPK3 in the glandular cells of stomachs under physiological condition. We have therefore conducted this study to immunohistochemically characterize the key element of necroptosis, RIPK3, in the mouse and human stomach. Results showed that RIPK3 positive cells could be observed in the surface mucosal cells, granular cells, and lamina propria cells in both mouse and human stomach tissues. Ratios of PCNA/RIPK3 positive cells in the glandular cells were ~ 2.1 in mouse and ~ 4.15 in human sections respectively. Morphological and double immunofluorescence analysis confirmed that these RIPK3 positive cells were mucous, parietal and lamina propria cells. Our results indicate that the expression of RIPK3 in different cell types might contribute to cell turnover of gastric mucosa in the mouse and human stomach under physiological condition.

Highlights

The relationship between cell death and human diseases has become a great interesting topic in research (Zhou and Yuan 2014)
We show a high rate of receptor-interacting protein kinase 3 (RIPK3) positive cells in mouse and human gastric specimens, RIPK3 was identified in different cell types such as surface mucous, fundic parietal and lamina propria cells in the stomachs
To estimate the turnover rate of glandular cells of gastric mucosa, we examined the proliferation activity labelled by PCNA and the expression of necroptosis key element RIPK3 with IHCs in mouse and human stomachs respectively

Summary

Introduction

The relationship between cell death and human diseases has become a great interesting topic in research (Zhou and Yuan 2014). The manner of cell death can be divided into two types: necrosis and programmed cell death (PCD). Necrosis is a passive cell death and can be regarded as an extreme cell clearance method in organisms caused by pathological factors such as physics, chemistry, and pathogens. PCD is an active process of cell self-regulation, mainly characterized by genetically controlled cellautonomous ordered death. People gradually realized that cell necrosis could occur in an orderly manner. This new cell death form was termed as necroptosis. Studies revealed that pro-inflammatory cytokines such as tumor necrosis factor (TNF)-α play an important stimulating role in the process of necroptosis (Laster et al 1988). TNF-α activates receptor-interacting protein kinase (RIPK) 1 (Moriwaki and Chan 2014; Silke et al 2015; Yu, 2015), and in turn activates mixed lineage kinase domain-like

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