Myosin light chain kinase mediates intestinal barrier disruption following burn injury.
Myosin light chain kinase mediates intestinal barrier disruption following burn injury.
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DOI：
10.1371/journal.pone.0034946
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Wang F
中科院分区：
文献类型：
--
作者：
Chen C;Wang P;Su Q;Wang S;Wang F
严重烧伤导致肠屏障功能丧失，但其机制尚不清楚。肌球蛋白轻链（MLC）激酶（MLCK）介导的MLC磷酸化在肠屏障功能的病理生理调节中至关重要。我们推测MLCK依赖的MLC磷酸化介导了烧伤后肠屏障功能的调节，MLCK抑制减轻了烧伤诱导的肠屏障功能障碍。将雄性balb/c小鼠随机分配至假烧伤（对照）或30%全身表面积（TBSA）全厚度烧伤，不腹膜内注射或腹膜内注射ML-9（2 mg/kg），MLCK抑制剂。测定了体内肠对异硫氰酸荧光素（FITC）-葡聚糖的渗透性。肠粘膜损伤进行了组织学评估。免疫荧光法检测紧密连接蛋白ZO-1、occludin和claudin-1。Western blot检测MLCK和磷酸化MLC在回肠黏膜中的表达。烧伤后肠粘膜通透性明显增加，并伴有粘膜损伤、紧密连接蛋白改变、MLCK和MLC磷酸化水平升高。用ML-9处理减弱了烧伤引起的肠通透性增加、粘膜损伤、紧密连接蛋白改变和MLC磷酸化降低，但MLCK表达没有减弱。MLCK依赖的MLC磷酸化介导严重烧伤后肠上皮屏障功能障碍这表明MLCK依赖的MLC磷酸化可能是治疗严重烧伤后肠上皮屏障破坏的关键靶点。
Severe burn injury results in the loss of intestinal barrier function, however, the underlying mechanism remains unclear. Myosin light chain (MLC) phosphorylation mediated by MLC kinase (MLCK) is critical to the pathophysiological regulation of intestinal barrier function. We hypothesized that the MLCK-dependent MLC phosphorylation mediates the regulation of intestinal barrier function following burn injury, and that MLCK inhibition attenuates the burn-induced intestinal barrier disfunction. Male balb/c mice were assigned randomly to either sham burn (control) or 30% total body surface area (TBSA) full thickness burn without or with intraperitoneal injection of ML-9 (2 mg/kg), an MLCK inhibitor. In vivo intestinal permeability to fluorescein isothiocyanate (FITC)-dextran was measured. Intestinal mucosa injury was assessed histologically. Tight junction proteins ZO-1, occludin and claudin-1 was analyzed by immunofluorescent assay. Expression of MLCK and phosphorylated MLC in ileal mucosa was assessed by Western blot. Intestinal permeability was increased significantly after burn injury, which was accompanied by mucosa injury, tight junction protein alterations, and increase of both MLCK and MLC phosphorylation. Treatment with ML-9 attenuated the burn-caused increase of intestinal permeability, mucosa injury, tight junction protein alterations, and decreased MLC phosphorylation, but not MLCK expression. The MLCK-dependent MLC phosphorylation mediates intestinal epithelial barrier dysfunction after severe burn injury. It is suggested that MLCK-dependent MLC phosphorylation may be a critical target for the therapeutic treatment of intestinal epithelial barrier disruption after severe burn injury.
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影响因子：
3.8
作者：
Finnerty, Celeste C.;Przkora, Rene;Herndon, David N.;Jeschke, Marc G.
通讯作者：
Jeschke, Marc G.
DOI：
10.1152/ajpgi.00412.2004
发表时间：
2005-03-01
影响因子：
4.5
作者：
Ma, TY;Boivin, MA;Said, HM
通讯作者：
Said, HM
影响因子：
3.8
作者：
Deitch, EA
通讯作者：
Deitch, EA
DOI：
10.1097/01.bcr.0000176878.79267.e8
发表时间：
2005-09-01
期刊：
JOURNAL OF BURN CARE & REHABILITATION
影响因子：
--
作者：
Magnotti, LJ;Deitch, EA
通讯作者：
Deitch, EA
影响因子：
2.8
作者：
Costantini, Todd W.;Eliceiri, Brian P.;Coimbra, Raul
通讯作者：
Coimbra, Raul