In this video collection, authors of findings published in The Journal of Clinical Investigation present personally guided tours of their results. The JCI accepts video submissions from authors of recently accepted manuscripts. Instructions can be found on the Author's Take Guidelines page.
Some patients with diabetes develop diabetic kidney disease (DKD), which can progress to a loss of renal function. High levels of TNF are predictive of disease and organ damage; however, it is not clear how elevated TNF promotes injury. In this episode, Alessia Fornoni reveals that TNF promotes free cholesterol–dependent podocyte apoptosis via an NFATc1/ ABCA1-dependent mechanism. The results of this study indicate that agents targeting cholesterol efflux should be further explored for treating proteinuric kidney diseases.
During sepsis, there is a progression from a hyperactive immune response to an immunosuppressive state that is characterized by macrophage reprogramming. However, the factors that drive this macrophage response are not well defined. In this episode, Dimitrios Balomenos and Gorjana Rackov discuss their recent study, which shows that p21 is instrumental in macrophage switching from a pro-inflammatory to an immunosuppressive state during sepsis. The results of this study reveal that p21 regulates the balance between p50-p50 and p65-p50 NF-κB during sepsis and provides a potential therapeutic target for this complex condition.
Psoriasis is a chronic inflammatory disease that is characterized by the presence of pruritic skin lesions. Aberrant interactions between the epithelia and immune system underlie the disease; however, the pathways that promote psoriasis are poorly understood. In this episode, Peter Marinkovich and Mårten Winge discuss their work, which shows that hyperactivation of RAC1 in the skin drives pathogenic interactions between the epidermis and the immune system in psoriasis. The results of this work suggest that RAC1 is a potential therapeutic target for this disease.
The skin serves as a powerful barrier against microbial, physical, and chemical insults and is maintained through constant proliferation and differentiation of epidermal cells. However, the mechanisms that regulate skin homeostasis are not fully understood. In this episode, Hisahiro Yoshida describes the development and characterization of a strain of mice that exhibit progressive pruritic dermatitis due to the presence of a mutation that results in hyperactivation of JAK1 tyrosine kinase. Treatment of these mice with JAK1 inhibitors delayed disease onset, indicating that JAK1-mediated signaling plays an important role in maintenance of skin barrier function.
Sex-specific differences have been observed in preclinical models of renal ischemic injury. In particular, females recover more readily from ischemia-reperfusion injury (IRI) than males, and testosterone has been shown to have a negative effect on renal ischemia tolerance. The factors that underlie these sex-dependent discrepancies are poorly understood, and it is not clear if these same differences extend to humans. In this episode, Matthew Levine and David Aufhauser describe the development of several murine renal ischemia and transplant models used to evaluate sex-specific effects on recovery after IRI. Their results demonstrate that recipient, not donor, sex determines transplantation outcomes. Moreover, evaluation of patient data from the United Network for Organ Sharing revealed that male recipients had increased delayed graft function compared to female recipients.