Highly pathogenic coronaviruses and the kidney.

Since the end of 2019, the outbreak of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has triggered a pneumonia epidemic, posing a significant public health challenge in 236 countries, territories, and regions worldwide. Clinically, in addition to the symptoms of pulmonary infection, many patients with SARS-CoV-2 infections, especially those with a critical illness, eventually develop multiple organ failure in which damage to the kidney function is common, ultimately leading to severe consequences such as increased mortality and morbidity. To date, three coronaviruses have set off major global public health security incidents: Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV), Middle East Respiratory Syndrome Coronavirus (MERS-CoV), and SARS-CoV-2. Among the diseases caused by the coronaviruses, the coronavirus disease 2019 (COVID-19) has been the most impactful and harmful. Similar to with SARS-CoV-2 infections, previous studies have shown that kidney injury is also common and prominent in patients with the two other highly pathogenic coronaviruses. Therefore, in this review, we aimed to comprehensively summarize the epidemiological and clinical characteristics of these three pandemic-level infections, provide a deep analysis of the potential mechanism of COVID-19 in various types of kidney diseases, and explore the causes of secondary kidney diseases of SARS-CoV-2, so as to provide a reference for further research and the clinical prevention of kidney damage caused by coronaviruses.

Caveolin-1 Alleviates Acetaminophen-Induced Hepatotoxicity in Alcoholic Fatty Liver Disease by Regulating the Ang II/EGFR/ERK Axis.

Acetaminophen (APAP) is a widely used antipyretic analgesic which can lead to acute liver failure after overdoses. Chronic alcoholic fatty liver disease (AFLD) appears to enhance the risk and severity of APAP-induced liver injury, and the level of angiotensin II (Ang II) increased sharply at the same time. However, the underlying mechanisms remain unclear. Caveolin-1 (CAV1) has been proven to have a protective effect on AFLD. This study aimed to examine whether CAV1 can protect the APAP-induced hepatotoxicity of AFLD by affecting Ang II or its related targets. In vivo, the AFLD model was established according to the chronic-plus-binge ethanol model. Liver injury and hepatic lipid accumulation level were determined. The levels of Angiotensin converting enzyme 2 (ACE2), Ang II, CAV1, and other relevant proteins were evaluated by western blotting. In vitro, L02 cells were treated with alcohol and oleic acid mixture and APAP. CAV1 and ACE2 expression was downregulated in APAP-treated AFLD mice compared to APAP-treated mice. The overexpression of CAV1 in mice and L02 cells alleviated APAP-induced hepatotoxicity in AFLD and downregulated Ang II, p-EGFR/EGFR and P-ERK/ERK expression. Immunofluorescence experiments revealed interactions between CAV1, Ang II, and EGFR. The application of losartan (an Ang II receptor antagonist) and PD98059 (an ERK1/2 inhibitor) alleviated APAP-induced hepatotoxicity in AFLD. In conclusion, our findings verified that CAV1 alleviates APAP-aggravated hepatotoxicity in AFLD by downregulating the Ang II /EGFR/ERK axis, which could be a novel therapeutic target for its prevention or treatment.