Morphogenetic lung defects of JSAP1-deficient embryos proceeds via the disruptions of the normal expressions of cytoskeletal and chaperone proteins.
Recent studies have shown that JNK/stress-activated protein kinase-associated protein 1 (JSAP1)-deficient mice die from respiratory failure shortly after birth. To understand the underlying mechanism, we investigated the histological appearances and cell type changes in developing jsap1(-/-) lungs between E12.5 and E18.5. At the light microscopic level, no overt abnormality was detected in jsap1(-/-) until E16.5. However, alveoli and airway formations that normally occur after E16.5 were poorly advanced in jsap1(-/-). Despite these morphological defects, surfactant secreting cells labeled by anti-SP-B or anti-SP-C were present in normal ranges in jsap1(-/-) lungs. Smooth muscle alpha-actin expressing cells were also developed in jsap1(-/-) lungs, although actin expression was decreased. The expressions of transcriptional factors, such as, nuclear factor Ib (Nfib), N-myc, and octamer transcriptional factor 1 (Oct-1), which play a critical role in lung morphogenesis, were found to be down-regulated, whereas signal transducer and activator of transcription 3 (Stat3), sonic hedgehog (Shh), and smoothened (Smo) were up-regulated, in jsap1(-/-) lungs at E17.5-E18.5 compared with those in jsap1(+/+) lungs. Proteomics analysis of E17.5 lung identified 39 proteins with altered expressions, which included actin, tropomyosin, myosin light chain, vimentin, heat shock protein (Hsp27), and Hsp84. These results suggest that JSAP1 is required for the normal expressions of cytoskeletal and chaperone proteins in the developing lung, and that impaired expressions of these proteins might cause morphogenetic defects observed in jsap1(-/-) lungs.
Ha
Hye-Yeong
HY
Division of Nano Sciences and Brain Disease Research Institute, Ewha Womans University, Seoul, Republic of Korea.
Kim
Jung-Bin
JB
Cho
Ik-Hyun
IH
Joo
Hyo-Jin
HJ
Kim
Kyoung-Shim
KS
Lee
Kang-Woo
KW
Sunwoo
Hongjai
H
Im
Joo-Young
JY
Lee
Ja-Kyeong
JK
Hong
Jang-Hee
JH
Han
Pyung-Lim
PL
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics*; D000818:Animals; D003598:Cytoskeletal Proteins / Q000235:genetics*; D015180:Electrophoresis, Gel, Two-Dimensional; D004622:Embryo, Mammalian / Q000378:metabolism; D005260:Female; D008168:Lung / Q000737:chemistry / Q000196:embryology* / Q000378:metabolism*; D051379:Mice; D018832:Molecular Chaperones / Q000235:genetics*; D009024:Morphogenesis; D009419:Nerve Tissue Proteins / Q000235:genetics*; D011247:Pregnancy
D048868:Adaptor Proteins, Signal Transducing; D003598:Cytoskeletal Proteins; C403619:Mapk8ip3 protein, mouse; D018832:Molecular Chaperones; D009419:Nerve Tissue Proteins