Interaction of Caveolin-3 and HCN is involved in the pathogenesis of diabetic cystopathy

Abstract

A growing body of research suggests that impaired bladder Cajal-like interstitial cells (ICCs) are a important component in the pathogenesis of diabetes-induced bladder dysfunction, although the molecular mechanisms have not been illustrated completely. The purpose of this study was to examine whether the hyperpolarization-activated cyclic nucleotide-gated (HCN) channels in ICCs-DM were responsible for the detrusor weak contractility of Diabetic cystopathy (DCP) and to study the possible mechanism of regulating the expression and function of HCN channels. HCN channels expression were decreased at the mRNA and protein levels. Forskolin (FSK), which can elevate intracellular cAMP levels, increased the density of the hyperpolarization-activated current and intracellular calcium concentration in both normal control (NC) rats and DCP rats, but the sensitivity of FSK on HCN channels was clearly down-regulated in DCP rats. The loss of caveolae and caveolin was in accordance with the decrease in HCN channels. Caveolin-3 co-localizes with and affects the expression and function of HCN. Taken together, these results indicate that the loss of caveolae and HCN channels in ICCs-DM is important in the pathogenesis of DCP. Increasing the number of caveolae to enhance the function of HCN channels may represent a viable target for the pharmacological treatment of DCP.

Time‐dependent functional, morphological, and molecular changes in diabetic bladder dysfunction in streptozotocin‐induced diabetic mice

“…DM is characterized by chronic hyperglycemia accompanied by numerous deleterious complications, including a series of lower urinary tract diseases . Diabetic bladder dysfunction (DBD) is a major DM complication in the lower urinary tract, affecting more than half of the patients with DM and causing a range of storage and voiding problems clinically. DBD was firstly defined by Frimodt‐Moller in 1976 and has been widely considered as some bladder dysfunction .…”

Cyclophosphamide-induced HCN1 channel upregulation in interstitial Cajal-like cells leads to bladder hyperactivity in mice

“…HCN channels were thought to be the key modulators of bladder ICC-LCs with respect to the conduction of bladder pacemaker activity. 12 In addition, HCN channel expression and function were significantly altered in the bladder ICC-LCs of diabetic cystopathy and detrusor overactive (DO) bladders with partial bladder outlet obstruction (PBOO), 21 , 22 suggesting that HCN channels in bladder ICC-LCs are involved in regulating bladder function in physiological and pathological conditions. To our knowledge, the role of HCN channels in bladder ICC-LCs in cystitis remains unknown.…”

Suo Quan Wan Protects Mouse From Early Diabetic Bladder Dysfunction by Mediating Motor Protein Myosin Va and Transporter Protein SLC17A9

“…DBD is a major lower urinary tract complication of diabetes and was first described by Moller (1976). Such complication is traditionally described as a triad of increased capacity, decreased sensation, and poor emptying (Daneshgari et al, 2006) and has affected over 50% of diabetic patients (Dong et al, 2016; Panigrahy et al, 2017). DBD development is divided into two phases: the compensated phase, which occurs in the early phase and is characterized by an OAB; and the decompensated phase, which occurs in the late phase and is characterized by an atonic bladder (Wang et al, 2009; Liu and Daneshgari, 2014).…”