Remodeling of lysosomal expression and regulation in thoracic and abdominal aorta of simulated weightless rats

  AIM  To investigate the remodeling of lysosomal expression and regulation in thoracic and abdominal aorta (TA and AA) in simulated weightlessness rats by hindlimb unloading tail suspension (HU) for 4 weeks.

  METHODS  Four weeks’ HU rat model was used to simulate the effect of weightlessness on the cardiovascular system. Western blotting, immunohistochemical staining and the quantitative real-time polymerase chain reaction (qRT-PCR) were conducted to examine the protein levels of lysosomal associated membrane protein 1 (LAMP1), transcription factor (TFEB), transcription factor E3 (TFE3) and the mRNA abundance of TFEB, TFE3 and lysosome related genes, including LAMP1, N-acylsphingosine amidohydrolase 1 (ASAH1), adenosine triphosphatase (ATPase) H+ transporting accessory protein 1 (ATP6AP1), ATPase H+ transporting V1 subunit H (ATP6V1H) and mucolipin 1 (MCOLN1) in TA and AA.

  RESULTS  Western blot analysis showed that compared with those in control (CTR) group, the protein levels of LAMP1 of both TA and AA were decreased in HU group (P<0.05). Immunohistochemical staining indicated that LAMP1 was mainly distributed in the intima and the media of TA and AA. Notably, after 4 weeks’ tail suspension, the protein level of LAMP1 in the intima of TA showed no significant difference, while it decreased evenly in the media (P<0.05). However, though the protein level of LAMP1 in the intima of AA showed no significant difference, it decreased unevenly in the media in HU rats (P<0.05). The protein expression of LAMP1 was higher in TA than that in AA either in the intima or the media in CTR group (P<0.05). qRT-PCR results showed that compared with that in CTR group, the mRNA abundance of lysosome related genes was increased in TA, but decreased in AA. The expressions of TFEB and TFE3 showed similar trend to those of lysosome related genes. Compared with those in CTR, the protein levels of TFEB and TFE3 were reduced both in TA and AA in HU rats, while the transcription levels of TFEB and TFE3 were increased in TA, but decreased in AA (P<0.05).

  CONCLUSION  The amount of lysosomal related proteins of both TA and AA is reduced in HU group, but the transcription levels of TFEB, TFE3 and lysosome related genes display region-specific remodeling, which may contribute to the remodeling of vascular wall.