Tubulointerstitial nephritis antigen-like 1 is a novel matricellular protein that promotes gastric bacterial colonization and gastritis in the setting of Helicobacter pylori infection

The interaction between the gastric epithelium and immune cells plays key roles in H. pylori-associated pathology. Here, we demonstrate a procolonization and proinflammatory role of tubulointerstitial nephritis antigen-like 1 (TINAGL1), a newly discovered matricellular protein, in H. pylori infection. Increased TINAGL1 production by gastric epithelial cells (GECs) in the infected gastric mucosa was synergistically induced by H. pylori and IL-1β via the ERK-SP1 pathway in a cagA-dependent manner. Elevated human gastric TINAGL1 correlated with H. pylori colonization and the severity of gastritis, and mouse TINAGL1 derived from non-bone marrow-derived cells promoted bacterial colonization and inflammation. Importantly, H. pylori colonization and inflammation were attenuated in Tinagl1−/− and Tinagl1ΔGEC mice and were increased in mice injected with mouse TINAGL1. Mechanistically, TINAGL1 suppressed CCL21 expression and promoted CCL2 production in GECs by directly binding to integrin α5β1 to inhibit ERK and activate the NF-κB pathway, respectively, which not only led to decreased gastric influx of moDCs via CCL21-CCR7-dependent migration and, as a direct consequence, reduced the bacterial clearance capacity of the H. pylori-specific Th1 response, thereby promoting H. pylori colonization, but also resulted in increased gastric influx of Ly6Chigh monocytes via CCL2-CCR2-dependent migration. In turn, TINAGL1 induced the production of the proinflammatory protein S100A11 by Ly6Chigh monocytes, promoting H. pylori-associated gastritis. In summary, we identified a model in which TINAGL1 collectively ensures H. pylori persistence and promotes gastritis.

Paleogene integrative stratigraphy and timescale of China

The Paleogene is the first period after the Mesozoic Mass Extinction. Mammals become the dominant group in the terrestrial ecosystem with a rapid radiation, and Asia has been considered to be the origin place of several mammalian groups.The Paleogene System consists mostly of terrestrial deposits in Asia, especially in East Asia. A well-established regional chronostratigraphic framework is the foundation for understanding both the Paleogene geologic history and evolutionary history of Asia and their relationships. The Paleogene is subdivided into the Paleocene, Eocene and Oligocene in the International Chronostratigraphic Chart. Based on the land mammal ages, the Chinese terrestrial Paleogene can be subdivided into 11 stages:the Shanghuan, Nongshanian and Bayanulanian stages of the Paleocene, the Lingchan, Arshantan, Irdinmanhan, Sharamurunian,Ulangochuian and Baiyinian stages of the Eocene, and the Ulantatalian and Tabenbulukian stages of the Oligocene. These stages have distinctive paleontological characters, with special significance of fossil mammals, which provide a reliable practical basis.The bases of the Shanghuan, Lingchan, and Ulantatalian stages are coincident respectively with those of the Paleocene, Eocene and Oligocene. The ages for their bases are determined as 66.0, 56.0 and 33.9 Ma, respectively, following that for the corresponding series in the International Chronostratigraphic Chart. For other stages, estimated ages are provided based on available paleomagnetic results.