Involvement of Matrix Metalloproteinases in COVID-19: Molecular Targets, Mechanisms, and Insights for Therapeutic Interventions.

MMPs are enzymes involved in SARS-CoV-2 pathogenesis. Notably, the proteolytic activation of MMPs can occur through angiotensin II, immune cells, cytokines, and pro-oxidant agents. However, comprehensive information regarding the impact of MMPs in the different physiological systems with disease progression is not fully understood. In the current study, we review the recent biological advances in understanding the function of MMPs and examine time-course changes in MMPs during COVID-19. In addition, we explore the interplay between pre-existing comorbidities, disease severity, and MMPs. The reviewed studies showed increases in different MMP classes in the cerebrospinal fluid, lung, myocardium, peripheral blood cells, serum, and plasma in patients with COVID-19 compared to non-infected individuals. Individuals with arthritis, obesity, diabetes, hypertension, autoimmune diseases, and cancer had higher MMP levels when infected. Furthermore, this up-regulation may be associated with disease severity and the hospitalization period. Clarifying the molecular pathways and specific mechanisms that mediate MMP activity is important in developing optimized interventions to improve health and clinical outcomes during COVID-19. Furthermore, better knowledge of MMPs will likely provide possible pharmacological and non-pharmacological interventions. This relevant topic might add new concepts and implications for public health in the near future.

Paternal Resistance Exercise Modulates Skeletal Muscle Remodeling Pathways in Fathers and Male Offspring Submitted to a High-Fat Diet.

Although some studies have shown that a high-fat diet (HFD) adversely affects muscle extracellular matrix remodeling, the mechanisms involved in muscle trophism, inflammation, and adipogenesis have not been fully investigated. Thus, we investigated the effects of 8 weeks of paternal resistance training (RT) on gene and protein expression/activity of critical factors involved in muscle inflammation and remodeling of fathers and offspring (offspring exposed to standard chow or HFD). Animals were randomly distributed to constitute sedentary fathers (SF; n = 7; did not perform RT) or trained fathers (TF n = 7; performed RT), with offspring from mating with sedentary females. After birth, 28 male pups were divided into four groups (n = 7 per group): offspring from sedentary father submitted either to control diet (SFO-C) or high-fat diet (SFO-HF) and offspring from trained father submitted to control diet (TFO-C) or high-fat diet (TFO-HF). Our results show that an HFD downregulated collagen mRNA levels and upregulated inflammatory and atrophy pathways and adipogenic transcription factor mRNA levels in offspring gastrocnemius muscle. In contrast, paternal RT increased MMP-2 activity and decreased IL-6 levels in offspring exposed to a control diet. Paternal RT upregulated P70s6k and Ppara mRNA levels and downregulated Atrogin1 mRNA levels, while decreasing NFκ-B, IL-1ß, and IL-8 protein levels in offspring exposed to an HFD. Paternal physical training influences key skeletal muscle remodeling pathways and inflammatory profiles relevant for muscle homeostasis maintenance in offspring submitted to different diets.