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Background Wound healing is a complex and dynamic process that includes 3 different phases: inflammation, proliferation, and remodeling. Kinins are vasoactive peptides released after tissue injury, and are directly involved in the development and maintenance of inflammatory processes, and their actions are mediated by the activation of receptors called B 1 and B 2 . Objective We aimed to evaluate the involvement of kinin receptors in the skin healing process. Methods Knockout mice for kinin receptors (KOB 1 , KOB 2 and KOB 1 B 2 ) and wild type controls (WT) were subjected to a skin excision model, and tissue repair process was evaluated during different phases of wound healing. Results In knockout animals for kinin receptors differences were observed in the resolution period of injury exceeding 17 days for the total closure of wounds. The absence of kinin receptors promotes a significant reduction in infiltration of polymorphonuclear cells on day 2 of the inflammatory phase. Already at the late stage of this phase (3 days) there was a negative influence on the infiltration of polymorphonuclear and mononuclear cells at the site of injury in comparison to WT. Collagen was significantly diminished in tissue of KOB 1 , KOB 2 and KOB 1 B 2 from day two to the end of the healing process. Moreover, wound tissue from KOB 2 and KOB 1 B 2 , but not KOB 1 , presented impaired parameters of re-epitheliazation, reduced proliferation of cells (PCNA immunostaining), and a lower number of myofibroblasts (α-SMA immunostaining). Conclusion These data reveal the involvement of kinin receptors in processes of skin repair. Both kinin receptors participate especially during the inflammatory phase, while B 2 receptors seem to be more relevant in the quality of the wound scar. Thus, a better understanding of the contribution of kinins to skin wound healing may reveal novel options for therapy. [ABSTRACT FROM AUTHOR]

Leptin is a hormone related to metabolism. It also influences blood pressure, but the mechanisms triggered in this process are not yet elucidated. Angiotensin-I converting enzyme (ACE) regulates cardiovascular functions and recently has been associated with metabolism control and obesity. Here, we used ob/ob mice, a model lacking leptin, to answer the question whether ACE and leptin could interact to influence blood pressure, thereby linking the renin-angiotensin system and obesity. These mice are obese and diabetic but have normal 24 h mean arterial pressure. Our results show that plasma and lung ACE activities as well as ACE mRNA expression were significantly decreased in ob/ob mice. In agreement with these findings, the hypotensive effect produced by enalapril administration was attenuated in the obese mice. Plasma renin, angiotensinogen, angiotensin I, bradykinin, and angiotensin 1–7 were increased, whereas plasma angiotensin II concentration was unchanged in obese mice. Chronic infusion of leptin increased renin activity and angiotensin II concentration in both groups and increased ACE activity in ob/ob mice. Acute leptin infusion restored ACE activity in leptin-deficient mice. Moreover, the effect of an ACE inhibitor on blood pressure was not changed in ob/+ mice during leptin treatment but increased four times in obese mice. In summary, our findings show that the renin–angiotensin system is altered in ob/ob mice, with markedly reduced ACE activity, which suggests a possible connection between the renin–angiotensin system and leptin. These results point to an important interplay between the angiotensinergic and the leptinergic systems, which may play a role in the pathogenesis of obesity, hypertension, and metabolic syndrome. [ABSTRACT FROM AUTHOR]

This study evaluated SARS-CoV-2 replication in human cell lines derived from various tissues and investigated molecular mechanisms related to viral infection susceptibility and replication. SARS-CoV-2 replication in BEAS-2B and A549 (respiratory tract), HEK-293 T (kidney), HuH7 (liver), SH-SY5Y (brain), MCF7 (breast), Huvec (endothelial) and Caco-2 (intestine) was evaluated by RT-qPCR. Concomitantly, expression levels of ACE2 (Angiotensin Converting Enzyme) and TMPRSS2 were assessed through RT-qPCR and western blot. Proteins related to autophagy and mitochondrial metabolism were monitored in uninfected cells to characterize the cellular metabolism of each cell line. The effect of ACE2 overexpression on viral replication in pulmonary cells was also investigated. Our data show that HuH7, Caco-2 and MCF7 presented a higher viral load compared to the other cell lines. The increased susceptibility to SARS-CoV-2 infection seems to be associated not only with the differential levels of proteins intrinsically related to energetic metabolism, such as ATP synthase, citrate synthase, COX and NDUFS2 but also with the considerably higher TMPRSS2 mRNA expression. The two least susceptible cell types, BEAS-2B and A549, showed drastically increased SARS-CoV-2 replication capacity when ACE2 was overexpressed. These modified cell lines are relevant for studying SARS-CoV-2 replication in vitro. Our data not only reinforce that TMPRSS2 expression and cellular energy metabolism are important molecular mechanisms for SARS-CoV-2 infection and replication, but also indicate that HuH7, MCF7 and Caco-2 are suitable models for mechanistic studies of COVID-19. Moreover, pulmonary cells overexpressing ACE2 can be used to understand mechanisms associated with SARS-CoV-2 replication. • HuH7, Caco-2 and MCF7 cells presented a high viral replication capacity compared to the other cell lines • These three cell lines presented differential levels of proteins related to energetic metabolism. • Cellular energy metabolism is an important factor for cell tropism and SARS-CoV-2 replication • The two least permissive cell types, BEAS-2B and A549, increased SARS-CoV-2 viral load when ACE2 was overexpressed. [ABSTRACT FROM AUTHOR]