LimKi-3 and Asthma

Current medical treatment for asthma aims to inhibit airway smooth muscle (ASM) contraction and proliferation, however, the efficacy of available treatment options is unsatisfactory. Therefore, we explored the effect of LIM domain kinase (LIMK) inhibitor - LIMKi3, on ASM to improve the understanding of ASM contraction and proliferation mechanisms, and to investigate new therapeutic targets.. Asthma model was induced in rats by intraperitoneal injection of ovalbumin. Using phospho-specific antibodies, we examined LIMK, phosphorylated LIMK, cofilin and phosphorylated cofilin. ASM contraction was studied in organ bath experiments. ASM cells proliferation was studied with cell counting kit-8 (CCK-8) and 5-ethynyl-2'-deoxyuridine (EdU) assays.. Immunofluorescence indicated that LIMKs are expressed in ASM tissues. Western blot revealed that LIMK1 and phospho-cofilin were significantly elevated in asthma ASM tissues. The LIMK inhibitor, LIMKi3 (1 ​μM) could reduce cofilin phosphorylation and therefore inhibit contraction of ASM tissues, and induce actin filament breakdown as well as cell proliferation reduction in cultured human ASM cells.. ASM contraction and proliferation in asthma may underlie the effects of LIMKs. Small molecule LIMK inhibitor, LIMKi3, might be a potential therapeutic strategy for asthma.

Topics: Actin Depolymerizing Factors; Animals; Asthma; Cell Proliferation; Humans; Lim Kinases; Muscle Contraction; Rats