Alteration in expression of myosin isoforms in detrusor smooth muscle following bladder outlet obstruction

Abstract

Partial urinary bladder outlet obstruction (PBOO) in men, secondary to benign prostatic hyperplasia, induces detrusor smooth muscle (DSM) hypertrophy. However, despite DSM hypertrophy, some bladders become severely dysfunctional (decompensated). Using a rabbit model of PBOO, we found that although DSM from sham-operated bladders expressed nearly 100% of both the smooth muscle myosin heavy chain isoform SM-B and essential light chain isoform LC17a, DSM from severely dysfunctional bladders expressed as much as 75% SM-A and 40% LC17b (both associated with decreased maximum velocity of shortening). DSM from dysfunctional bladder also exhibited tonic-type contractions, characterized by slow force generation and high force maintenance. Immunofluorescence microscopy showed that decreased SM-B expression in dysfunctional bladders was not due to generation of a new cell population lacking SM-B. Metabolic cage monitoring revealed decreased void volume and increased voiding frequency correlated with overexpression of SM-A and LC17b. Myosin isoform expression and bladder function returned toward normal upon removal of the obstruction, indicating that the levels of expression of these isoforms are markers of the PBOO-induced dysfunctional bladders.

SM2+/- male mice are predisposed to develop urinary tract obstruction and hyper contractility of the bladder smooth muscle upon ageing

“…However, the expression level of SM2 alters in a variety of pathological conditions. For example, decreased expression of SM2 has been reported in obstructed urinary bladder of rabbit and rat (Chacko and Longhurst, 1994;Wang et al, 1995;Cher et al, 1996;Gomes et al, 2000;Lin et al, 2000;DiSanto et al, 2003;Austin et al, 2004), in pulmonary arteries of primary pulmonary hypertension (Packer et al, 1998;Itoh et al, 2002), and in neointimal smooth muscle cells of injured or atherosclerotic vessels (Aikawa et al, 1993). On the other hand, in myometrium of ovariectomized rabbits SM2 has been found to increase, yet such an alteration can be normalized by estrogen treatment (Capriani et al, 1997).…”

Mechanical stretch upregulates proteins involved in Ca2+ sensitization in urinary bladder smooth muscle hypertrophy

“…partial bladder outlet obstruction; cell stretch; human bladder; benign prostatic hyperplasia; calcium sensitization DETRUSOR SMOOTH MUSCLE (DSM) hypertrophy is associated with alteration of the signaling pathways that initiate and maintain force in the bladder wall smooth muscle during partial bladder outlet obstruction (pBOO). These alterations have been observed in animal models and men with benign prostatic hyperplasia (BPH)-induced obstruction (7,9,14,19). In both animal models and humans, removal of the obstruction causes regression of smooth muscle hypertrophy, and the bladder function returns relatively to normal in most instances.…”

“…These alterations have been observed in animal models and men with benign prostatic hyperplasia (BPH)-induced obstruction (7,9,14,19). In both animal models and humans, removal of the obstruction causes regression of smooth muscle hypertrophy, and the bladder function returns relatively to normal in most instances.…”

Transcriptional Repression of Caveolin-1 (CAV1) Gene Expression by GATA-6 in Bladder Smooth Muscle Hypertrophy in Mice and Human Beings

“…These compensatory changes help to maintain close to normal bladder function in some cases. However, in some animals and men, these compensatory changes are not sufficient to restore normal bladder function, [1][2][3] eventually leading to severe bladder dysfunction (decompensation). These compensatory changes are associated with altered expression of contractile proteins and various signaling and regulatory proteins such as Rho-activated kinase and caveolins.…”

“…These compensatory changes are associated with altered expression of contractile proteins and various signaling and regulatory proteins such as Rho-activated kinase and caveolins. [3][4][5][6] Caveolins are members of a family of integral membrane proteins that are the principal components of caveolae, which are 50-to 100-nm flask-shaped invaginations present in a variety of cells including endothelial cells, adipocytes, cardiac myocytes, and smooth muscle cells (SMCs). Caveolae are a morphologically identifiable subset of lipid rafts that are involved in numerous cellular processes including vesicular transport, cholesterol ho-meostasis, and signal transduction.…”