title: Airways in smooth muscle α-actin null mice experience a compensatory mechanism that modulates their contractile response.
abstract: We hypothesized that ablation of smooth muscle α-actin (SM α-A), a contractile-cytoskeletal protein expressed in airway smooth muscle (ASM) cells, abolishes ASM shortening capacity and decreases lung stiffness. In both SM α-A knockout and wild-type (WT) mice, airway resistance (Raw) determined by the forced oscillation technique rose in response to intravenous methacholine (Mch). However, the slope of Raw (cmH(2)O·ml(-1)·s) vs. log(2) Mch dose (μg·kg(-1)·min(-1)) was lower (P = 0.007) in mutant (0.54 ± 0.14) than in WT mice (1.23 ± 0.19). RT-PCR analysis performed on lung tissues confirmed that mutant mice lacked SM α-A mRNA and showed that these mice had robust expressions of both SM γ-A mRNA and skeletal muscle (SKM) α-A mRNA, which were not expressed in WT mice, and an enhanced SM22 mRNA expression relative to that in WT mice. Compared with corresponding spontaneously breathing mice, mechanical ventilation-induced lung mechanical strain increased the expression of SM α-A mRNA in WT lungs; in mutant mice, it augmented the expressions of SM γ-A mRNA and SM22 mRNA and did not alter that of SKM α-A mRNA. In mutant mice, the expression of SM γ-A mRNA in the lung during spontaneous breathing and its enhanced expression following mechanical ventilation are consistent with the likely possibility that in the absence of SM α-A, SM γ-A underwent polymerization and interacted with smooth muscle myosin to produce ASM shortening during cholinergic stimulation. Thus our data are consistent with ASM in mutant mice experiencing compensatory mechanisms that modulated its contractile muscle capacity.
authors: F. R. Shardonofsky, Scott & White Children’s Hospital, 2401 31st St., MS 27-134, Temple, TX 76508, USA. fshardonofsky@swmail.sw.org
authors: Felix R
authors: FR
authors: Shardonofsky
authors: Joan
authors: J
authors: Moore
authors: Robert J
authors: RJ
authors: Schwartz
authors: Aladin M
authors: AM
authors: Boriek
mesh_terms: D000199:Actins / Q000235:genetics* / Q000378:metabolism*; D000403:Airway Resistance / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D000818:Animals; D003285:Contractile Proteins / Q000235:genetics / Q000378:metabolism; D008168:Lung / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology*; D016210:Methacholine Chloride / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008840:Microfilament Proteins / Q000235:genetics / Q000378:metabolism; D009119:Muscle Contraction / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D009124:Muscle Proteins / Q000235:genetics / Q000378:metabolism; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D009130:Muscle, Smooth / Q000378:metabolism* / Q000502:physiology*; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D012333:RNA, Messenger / Q000235:genetics; D012121:Respiration, Artificial / Q000379:methods; D024745:Smooth Muscle Myosins / Q000187:drug effects / Q000235:genetics / Q000378:metabolism / Q000502:physiology
chemical_list: D000199:Actins; D003285:Contractile Proteins; D008840:Microfilament Proteins; D009124:Muscle Proteins; D012333:RNA, Messenger; C544013:alpha-smooth muscle actin, mouse; C051615:transgelin; D016210:Methacholine Chloride; D024745:Smooth Muscle Myosins