Tissue inhibitors of metalloproteinases (TIMPs) suppress matrix metalloproteinase (MMP) activity critical for extracellular matrix turnover associated with both physiologic and pathologic tissue remodeling. We demonstrate here that TIMP-2 abrogates angiogenic factor-induced endothelial cell proliferation in vitro and angiogenesis in vivo independent of MMP inhibition. These effects require alpha 3 beta 1 integrin-mediated binding of TIMP-2 to endothelial cells. Further, TIMP-2 induces a decrease in total protein tyrosine phosphatase (PTP) activity associated with beta1 integrin subunits as well as dissociation of the phosphatase SHP-1 from beta1. TIMP-2 treatment also results in a concomitant increase in PTP activity associated with tyrosine kinase receptors FGFR-1 and KDR. Our findings establish an unexpected, MMP-independent mechanism for TIMP-2 inhibition of endothelial cell proliferation in vitro and reveal an important component of the antiangiogenic effect of TIMP2 in vivo.

Coronavirus-19 (COVID-19) caused by SARS-CoV-2 has become a global pandemic. Risk of transmission may occur during endoscopy and the goal is to prevent infection among healthcare professionals while providing essential services to patients. Asia was the first continent to have a COVID-19 outbreak, and this position statement of the Asian Pacific Society for Digestive Endoscopy shares our successful experience in maintaining safe and high-quality endoscopy practice at a time when resources are limited. Sixteen experts from key societies of digestive endoscopy in Asia were invited to develop position statements, including patient triage and risk assessment before endoscopy, resource prioritisation and allocation, regular monitoring of personal protective equipment, infection control measures, protective device training and implementation of a strategy for stepwise resumption of endoscopy services after control of the COVID-19 outbreak.

In recent years a peculiar type of chronic pancreatitis with underlying autoimmunity has been described. Lymphoplasmacytic infiltration and fibrosis on histology and elevated IgG levels or detected autoantibodies on laboratory data support the concept of autoimmune chronic pancreatitis (AIP). Pancreatic imaging reveals a rare association of diffuse enlargement of the pancreas and irregular narrowing of the main pancreatic duct, which is unique and specific to AIP. Although AIP is not a common disease, it is increasingly being recognized as knowledge of this entity builds up. Clinically it is very important to be aware of this disease because AIP can clinically disguise as pancreaticobiliary malignancies, ordinary chronic, or acute pancreatitis. Above all, AIP is a very attractive disease to clinicians in terms of its dramatic response to oral steroid therapy in contrast to ordinary chronic pancreatitis. This review discusses the clinical, laboratory, histologic, and imaging findings that are seen in patients with AIP, especially focusing on the diagnosis.