L-selectin on leukocyte surfaces mediates cell rolling on endothelium. L-selectin blockade with antibodies attenuated ischemic-reperfusion injury (IRI) in heart and skeletal muscle, but its role in renal IRI is unknown. We evaluated the role of L-selectin in renal IRI using L-selectin-deficient mice. Neutrophil migration to chemically inflamed peritoneum was reduced by 47% (P < 0.01) in L-selectin-deficient mice. Ischemia was induced by bilateral renal pedicle clamping for 30 min. Control and L-selectin groups had similar elevations of serum creatinine (1.8 +/- 0.3 vs. 1.7 +/- 0.2 mg/dl) and blood urea nitrogen (111 +/- 17 vs. 128 +/- 12 mg/dl) 24 h postischemia. Pathological assessment showed comparable degrees of tubular necrosis at 24 h. The postischemic increase in peritubular neutrophils per 10 high-power field was similar in control and L-selectin-deficient groups at 4 (28 +/- 10 vs. 22 +/- 5), 12 (245 +/- 80 vs. 236 +/- 78), and 24 h (130 +/- 12 vs. 156 +/- 18). These data argue against a significant role for L-selectin in renal IRI. Patho-physiological roles of L-selectin in vivo appear to be more complex than in vitro data would suggest.
The heavily labeled LRCs, located exclusively in the central region, represent cells that divide very infrequently during homeostasis (putative stem cells); on perturbation, these cells can proliferate. The lightly labeled LRCs, located in the central and germinative zones, cycle more frequently than the heavily labeled ones. These LRCs may be phenotypically indistinguishable from stem cells and maintain the normal proliferative needs of the lens. A third population of actively cycling cells exists primarily in the germinative zone and represents the transit amplifying cells, which have a limited proliferative potential.
Acute myocardial infarction (AMI), as the first manifestation of ischemic heart disease, is the most common cause of death in developed countries. A recent study showed that metastasis associated lung adenocarcinoma transcript 1 (MALAT1), a prognostic marker for lung cancer metastasis, could promote myocardial ischemia-reperfusion injury by regulating the levels of microRNA (miR)-145. In order to elucidate the biological function of MALAT1 in the pathogenesis of AMI and to explore the mechanisms underlying its action, an AMI rat model was established by ligation of the left anterior descending coronary artery. Downregulation of MALAT1 by siRNA transfection attenuated heart damage in an AMI model rat. The mouse cardiomyocyte cell line HL-1 was used to show that downregulation of nucleotide binding and oligomerization domain-like receptor C5 (NLRC5) and upregulation of miR-125b-5p were the results of MALAT1 silencing. TargetScan and a dual-luciferase reporter assay indicated that NLRC5 is a direct target of miR-125b-5p. Overexpression of miR-125b-5p significantly reduced hypoxia/reperfusion-induced apoptosis of HL-1 cells, an effect that could be blocked by NLCR5 overexpression. Taken together, these results suggest that MALAT1 reduced the protective effect of miR-125b-5p on injured cells through upregulation of NLCR5. This study highlights the role of MALAT1 in the pathogenesis of AMI and may guide future genetic therapeutic strategies for AMI treatment.
Long noncoding RNAs (lncRNAs) are involved in multiple nervous system diseases, including neuropathic pain. Previous studies have demonstrated that lncRNA metastasis‐associated lung adenocarcinoma transcript 1 (MALAT1) has been identified as a diagnostic biomarker in many diseases. Nevertheless, the function of MALAT1 in neuropathic pain progression is still unclear. Here, we established a chronic constriction injury (CCI) rat model. We found that MALAT1 was remarkably upregulated in CCI rats. In addition, neuropathic pain behaviors such as mechanical and thermal hyperalgesia were reduced by the inhibition of MALAT1. Meanwhile, the loss of MALAT1 was able to depress the neuroinflammation process via the inhibition of COX‐2, interleukin‐1β, and interleukin‐6. A previous study has indicated that miR‐206 upregulation can restrain the CCI‐induced neuropathic pain. Furthermore, we exhibited that miR‐206 was significantly downregulated and silence of MALAT1 restrained its expression in CCI rats. For another, ZEB2 was a target of miR‐206 and it was shown that ZEB2 was elevated in CCI rats in a time‐dependent manner. Overexpression of miR‐206 obviously suppressed ZEB2 levels in rat microglial cells. Subsequently, it was demonstrated that upregulation of miR‐206 rescued the neuropathic pain triggered by ZEB2 overexpression in vivo through neuroinflammation inhibition. Overall, we indicated that suppression of MALAT1 ameliorated neuropathic pain progression via miR‐206/ZEB2 axis.
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