sj-docx-2-jdr-10.1177_00220345231198448 – Supplemental material for Circ-Slain2 Alleviates Cartilage Degradation and Inflammation of TMJOA

Supplemental material, sj-docx-2-jdr-10.1177_00220345231198448 for Circ-Slain2 Alleviates Cartilage Degradation and Inflammation of TMJOA by X. Pan, Z. Zhao, X. Huang and X. Cen in Journal of Dental Research</p

sj-pdf-1-jdr-10.1177_00220345231198448 – Supplemental material for Circ-Slain2 Alleviates Cartilage Degradation and Inflammation of TMJOA

Supplemental material, sj-pdf-1-jdr-10.1177_00220345231198448 for Circ-Slain2 Alleviates Cartilage Degradation and Inflammation of TMJOA by X. Pan, Z. Zhao, X. Huang and X. Cen in Journal of Dental Research</p

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

The significant improvements in siRNA therapy have been achieved, which have great potential applications in humans. The kidney is a comparatively easy target organ of siRNA therapy due to its unique structural and functional characteristics. Here, we reviewed recent achievements in siRNA design, delivery and application with focuses on kidney diseases, in particular kidney transplant-related injuries. In addition, the strategy for increasing serum stability and immune tolerance of siRNA was also discussed. At last, the future challenges of siRNA therapy including organ/tissue/cell-specific delivery and time-controlled silence, as well as selecting therapeutic targets, were addressed as well

Increased peripheral and local soluble FGL2 in the recovery of renal ischemia reperfusion injury in a porcine kidney auto-transplantation model

BACKGROUND: Regulatory T cells (Treg) protect kidney against ischemia reperfusion (IR) injury via suppressing innate immunity, but the mechanism has not been fully clarified. Soluble fibrinogen-like protein 2 (sFGL2), a novel effector of Treg, may affect apoptosis and inflammation. This study investigated the role of sFGL2 in renal IR injury in a porcine kidney auto-transplantation model. MATERIALS AND METHODS: The left kidney was retrieved from mini pigs and infused by University of Wisconsin solution into the renal artery with the renal artery and vein clamped for 24-h cold storage. After the right nephrectomy, the left kidney was auto-transplanted into the right for 2 weeks. 3 pigs were sacrificed at day 2, 5, 7, 10 and 14 post-transplantation respectively. Collected renal tissues and daily blood samples were stored for further analyses. RESULTS: Both serum creatinine and blood urea nitrogen were maximized during day 2 to 5 and followed by a gradual recovery over 2 weeks. The similar pattern were showed in histological damage, myeloperoxidase + cells and apoptosis in the kidney, as well as circulating TNF-α and IFN-γ. Serum sFGL2 presented a fluctuating increase and reached a peak at day 10. The expression of sFGL2 and its receptor FcγRIIB as well as Foxp3 and IL-10 in the kidney was notably increased from day 5 to 10. CONCLUSION: The increased sFGL2 together with FcγRIIB during renal recovery after IR injury suggested that sFGL2 might be a potential renoprotective mediator involved in the renal self-repairing and remodeling in this 2-week porcine auto-transplantation model

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

BACKGROUND: The naked caspase-3 small interfering RNA (siRNA) infused into the renal artery during cold preservation was effective, but did not protect auto-transplant porcine kidneys with increased inflammation and apoptosis in our previous study. The mechanisms involved, in particular, whether siRNA or complementary systemic feedback eliciting innate immune responses are worthy to be further investigated. METHODS: The protein and mRNA expression of innate immunity-related molecules were detected by western blotting and quantitative PCR in the tissues previously collected from 48 h auto-transplant kidneys. The donor kidneys were retrieved from mini pigs and cold preserved by University of Wisconsin solution with/without 0.3 mg caspase-3 siRNA for 24 h. RESULTS: The protein level of Toll like receptor (TLR) 3, TLR7, and their main adapters, TRIF and MyD88, was up-regulated in the siRNA preserved auto-transplant kidneys. The mRNA level of NF-κB and c-Jun was increased, as well as pro-inflammatory cytokines, including IL-1β, IL-6, TNF-α and interferon (IFN)-α, β and γ. In addition, the non-TLR RNA sensor PKR protein, but not RIG1, was also increased in the siRNA preserved auto-transplant kidneys. CONCLUSIONS: The activation of innate immunity with amplified inflammatory responses in the caspase-3 siRNA preserved auto-transplant kidneys are associated with increased TLR3, TLR7 and PKR, which might be due to complementary systemic feedback, although persistent actions initiated by short-acting caspase-3 siRNA cannot be completely ruled out. These results provided valuable evidence to guide future siRNA design and pre-clinic studies