Simulated physiological stretch-induced proliferation of human bladder smooth muscle cells is regulated by MMPs

Bu, Siyuan; Zhu, Ye; Peng, Chuandu; Cai, Xiang; Cao, Canhui; Tan, Hong; Cheng, Jingqiu; Zhang, Jie; Liu, Jiaming; Li, Hong; Wang, Kun‐Jie

doi:10.1016/j.abb.2014.09.012

Cited by 7 publications

(3 citation statements)

References 35 publications

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“…3d ). Several studies suggested that mechanical stimulation is involved in the regulation of MMPs in some organs, such as human bladder smooth muscle cells 54 , musculoskeletal progenitors 55 , or even some ocular tissues, including sclera fibroblasts 56 , trabecular meshwork 57 and lamina cribrosa cells 58 . To further investigate the role of mechanical stretch in altered transcriptional signatures of keratoconus stromal cells, we performed cyclical mechanical stimulation on a human stromal keratocyte cell line, HTK cells (Fig.…”

Section: Resultsmentioning

confidence: 99%

Single-cell atlas of keratoconus corneas revealed aberrant transcriptional signatures and implicated mechanical stretch as a trigger for keratoconus pathogenesis

et al. 2022

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Keratoconus is a common ectatic corneal disorder in adolescents and young adults that can lead to progressive visual impairment or even legal blindness. Despite the high prevalence, its etiology is not fully understood. In this study, we performed single-cell RNA sequencing (scRNA-Seq) analysis on 39,214 cells from central corneas of patients with keratoconus and healthy individuals, to define the involvement of each cell type during disease progression. We confirmed the central role of corneal stromal cells in this disease, where dysregulation of collagen and extracellular matrix (ECM) occurred. Differential gene expression and histological analyses revealed two potential novel markers for keratoconus stromal cells, namely CTSD and CTSK. Intriguingly, we detected elevated levels of YAP1 and TEAD1, the master regulators of biomechanical homeostasis, in keratoconus stromal cells. Cyclical mechanical experiments implicated the mechanical stretch in prompting protease production in corneal stromal cells during keratoconus progression. In the epithelial cells of keratoconus corneas, we observed reduced basal cells and abnormally differentiated superficial cells, unraveling the corneal epithelial lesions that were usually neglected in clinical diagnosis. In addition, several elevated cytokines in immune cells of keratoconus samples supported the involvement of inflammatory response in the progression of keratoconus. Finally, we revealed the dysregulated cell-cell communications in keratoconus, and found that only few ligand-receptor interactions were gained but a large fraction of interactional pairs was erased in keratoconus, especially for those related to protease inhibition and anti-inflammatory process. Taken together, this study facilitates the understanding of molecular mechanisms underlying keratoconus pathogenesis, providing insights into keratoconus diagnosis and potential interventions.

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Section: Resultsmentioning

confidence: 99%

Single-cell atlas of keratoconus corneas revealed aberrant transcriptional signatures and implicated mechanical stretch as a trigger for keratoconus pathogenesis

et al. 2022

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“…Our team previously studied the long-term effect of BOO on bladder smooth muscle cells and HUCs using two models. [21][22][23][24] In the present experiment, HUCs were treated with 70 cm H 2 O for 6 hours to simulate pathological HP.…”

Section: Discussionmentioning

confidence: 99%

β‐Adrenoceptors regulate matrix metalloproteinase expression in human urothelial cells under hydrostatic pressure

Lan

Jin

et al. 2020

Neurourology and Urodynamics

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The bladder wall is constantly subjected to intravesical pressure during the filling and voiding cycles. An imbalance between matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) under elevated intravesical pressure contributes to pathological changes in the bladder. To investigate the changes in human urothelial cells (HUCs) under elevated intravesical pressure, this study analyzed the effect of β‐adrenoceptor signaling on the expression of MMPs and TIMPs in HUCs exposed to pathological hydrostatic pressure (HP) (70 cm H2O) for 6 hours. Quantitative polymerase chain reaction, Western blot analysis, and cell fluorescence staining were used to explore the effect of β‐adrenoceptor signaling on the expression of MMPs and TIMPs in HUCs after agonist and/or antagonist treatment. The expression levels of β2‐ and β3‐adrenoceptor, MMP1, and MMP2 were greatly downregulated, while the expression of TIMP1 was greatly upregulated. Formoterol and BRL 37344, which are agonists of β2‐ and β3‐adrenoceptor, respectively, significantly increased MMP1 and MMP2 expression under 70 cm H2O. As a classic downstream pathway of β2‐ and β3‐adrenoceptor, protein kinase A (PKA) signaling inhibited MMP1 and MMP2 expression by regulating cAMP response element binding protein (CREB) activity. MMP1 and MMP2 expression in HUCs under 70 cm H2O was modified by β2‐ and β3‐adrenoceptor via the PKA/CREB pathway. This outcome suggests that MMPs likely participate in the pathological effects of elevated intravesical pressure. The underlying mechanism of β2‐ and β3‐adrenoceptor in elevated intravesical pressure was also revealed; this mechanism constitutes a new potential therapeutic target for partial bladder outlet obstruction.

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“…In addition to the urothelium, the impact of mechanical stretch on other cell types such as smooth muscle cells (SMCs) isolated from the bladder has been explored. Bu et al demonstrated that stretch-induced proliferation of SMCs correlated with the upregulation of metalloproteinases (MMPs) MMP-1, 2, 3, and 7 under 10% and 15% stretch conditions in a stretch-dependent manner (Bu et al, 2014). Other studies have explored the impact of stretch on SMCs, demonstrating the importance of this mechanical stimulus for aspects of the bladder beyond the urothelium (McDermott et al, 2013;Zheng et al, 2016;Pingyu et al, 2019).…”

Section: Models Incorporating Urothelial Stretchmentioning

confidence: 99%

Recurrent Urinary Tract Infection: A Mystery in Search of Better Model Systems

Murray

Flores

Williams

et al. 2021

Front. Cell. Infect. Microbiol.

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Urinary tract infections (UTIs) are among the most common infectious diseases worldwide but are significantly understudied. Uropathogenic E. coli (UPEC) accounts for a significant proportion of UTI, but a large number of other species can infect the urinary tract, each of which will have unique host-pathogen interactions with the bladder environment. Given the substantial economic burden of UTI and its increasing antibiotic resistance, there is an urgent need to better understand UTI pathophysiology – especially its tendency to relapse and recur. Most models developed to date use murine infection; few human-relevant models exist. Of these, the majority of in vitro UTI models have utilized cells in static culture, but UTI needs to be studied in the context of the unique aspects of the bladder’s biophysical environment (e.g., tissue architecture, urine, fluid flow, and stretch). In this review, we summarize the complexities of recurrent UTI, critically assess current infection models and discuss potential improvements. More advanced human cell-based in vitro models have the potential to enable a better understanding of the etiology of UTI disease and to provide a complementary platform alongside animals for drug screening and the search for better treatments.

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Simulated physiological stretch-induced proliferation of human bladder smooth muscle cells is regulated by MMPs

Cited by 7 publications

References 35 publications

Single-cell atlas of keratoconus corneas revealed aberrant transcriptional signatures and implicated mechanical stretch as a trigger for keratoconus pathogenesis

Single-cell atlas of keratoconus corneas revealed aberrant transcriptional signatures and implicated mechanical stretch as a trigger for keratoconus pathogenesis

β‐Adrenoceptors regulate matrix metalloproteinase expression in human urothelial cells under hydrostatic pressure

Recurrent Urinary Tract Infection: A Mystery in Search of Better Model Systems

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