Naked caspase 3 small interfering RNA is effective in cold preservation but not in autotransplantation of porcine kidneys

The protective effect of nesfatin-1 against renal ischemia–reperfusion injury in rats

“…Previous study reported that caspase-3, which is regarded as a pivotal indicator of apoptosis, had an important role in the process of apoptosis in renal I/R injury models. 37,38 Nesfatin-1 has been reported to inhibit active caspase-3 expression in vivo.…”

Fighting against kidney diseases with small interfering RNA: opportunities and challenges

“…Therefore, large animal models, such as porcine models, are indispensable to compensate for the limitations of rodent models due to their greater similarity to human beings. The investigations on siRNA conducted in our laboratory have reflected this trend in the field [14,18,22]. …”

“…In our previous research, the unmodified naked caspases-3 siRNAs aggravated renal graft injury [14]. A potential reason for this effect is due to the kidney structure.…”

“…Because siRNA is highly efficient at gene silencing, it is possible to develop specific siRNA-based drugs that could target any genes, including those that have no known pharmacological antagonists or inhibitors. Different types of synthetic siRNA have been tested for their efficacy in various disease models, including cancer [8,9], autoimmune disorders [10], cardiovascular injuries [11,12], and organ transplantation [13,14], including native and transplanted kidney injuries [15]. …”

Innate immunity activation involved in unprotected porcine auto-transplant kidneys preserved by naked caspase-3 siRNA

“…Moreover, the treatment of recipient could be avoided, if the local administration of siRNA during donor preservation is enough to protect the transplant kidney. Therefore, the naked caspase-3 siRNA was infused into the renal artery during cold preservation, in which the caspase-3 siRNA was effective in terms of reducing caspase-3 mRNA and protein, but did not protect the siRNA preserved auto-transplant kidneys after 48 h, even increased caspase-3 expression, inflammation, apoptosis and renal tissue damage [4]. However, the mechanisms involved are not clear and worthy to be further investigated.…”