Expression of smooth muscle myosin isoforms in urinary bladder smooth muscle during hypertrophy and regression.
BACKGROUND
Partial ligation of the urinary out-flow tract of rabbit bladder induces hypertrophy of the smooth muscle layer in the bladder wall, and it is reversible by the removal of the ligature. The expression of smooth muscle myosin heavy chain isoforms SM1 and SM2 after hypertrophy and the regression of hypertrophy (reversal) was investigated at the translational and transcriptional levels using this experimental model.


METHODS
The contractile activity of smooth muscle strips derived from normal, hypertrophied, and reversal bladders was measured using electrical stimulation. Expression of SM1 and SM2 in normal, hypertrophied, and reversal muscle tissue was characterized using SDS-PAGE, reverse transcriptase-PCR (RT-PCR), and RNase protection assay.


RESULTS
Smooth muscle strips from hypertrophied urinary bladder revealed a decrease in both force and rate of force generation in response to field stimulation. These alterations in contractility were reversed by removal of the obstruction. The altered function in bladder hypertrophy was also associated with changes in translation and transcription of the smooth muscle heavy chain isoforms SM1 and SM2. Upon regression of the hypertrophy by removal of the obstruction, the relative ratio of myosin heavy chain SM2:SM1 returned to nearly normal values. Analyses by RT-PCR showed a decrease in the mRNA transcript for SM2 in hypertrophied bladder muscle; and, on reversal of the hypertrophy, the SM2 mRNA level returned to that of normal bladder. These data suggest that the obstruction-induced hypertrophy activates a down-regulating mechanism for the expression of myosin SM2 heavy chain.


CONCLUSIONS
Obstruction-induced alteration in the contractile characteristics of the urinary bladder smooth muscle is associated with changes in the expression of smooth muscle myosin heavy chains at both the protein and mRNA levels. The contractile function and the myosin heavy chain expression return to normal after regression of the smooth muscle hypertrophy on removal of the obstruction.
Wang
Z E
ZE
Department of Pathobiology, University of Pennsylvania, Philadelphia, USA.
Gopalakurup
S K
SK
Levin
R M
RM
Chacko
S
S
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D015536:Down-Regulation / Q000502:physiology; D006984:Hypertrophy / Q000378:metabolism; D008297:Male; D008969:Molecular Sequence Data; D009130:Muscle, Smooth / Q000737:chemistry* / Q000502:physiology*; D015879:Myosin Subfragments / Q000096:biosynthesis*; D012333:RNA, Messenger / Q000032:analysis; D011817:Rabbits; D012074:Remission Induction; D001743:Urinary Bladder / Q000737:chemistry / Q000378:metabolism* / Q000473:pathology*
D015879:Myosin Subfragments; D012333:RNA, Messenger