Conditional Mutation of Pkd2 Causes Cystogenesis and Upregulates β-Catenin

Kim, Ingyu; Ding, Tan; Fu, Yulong; Li, Cunxi; Cui, Lan; Li, Ao; Lian, Peiwen; Liang, Dan; Wang, Dao Wen; Guo, Caiying; Ma, Jie; Zhao, Ping; Coffey, Robert J.; Zhan, Qimin; Wu, Guanqing

doi:10.1681/asn.2009030271

Cited by 76 publications

(85 citation statements)

References 66 publications

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“…pyramidal neuronal death and post-ischemic memory impairment after transient ischemic brain injury · anti-allodynic effect in inflammatory and neuropathic pain · reduced salivary gland function after radiotherapy Knowles et al, 2011;Liu et al, 2013;So et al, 2015;Tan and McNaughton, 2016 · cysts in kidney and pancreas · defects in cardiac septum · focal haemorrhage · total body edema · male reproductive tract defects · embryonic lethality Boulter et al, 2001;Kim et al, 2009;Nie and Arend, 2014;Wu et al, 1998 …”

Section: Wwwecmjournalorg O Krupkova Et Al Trp Channels In Joint Dmentioning

confidence: 99%

The role of transient receptor potential channels in joint diseases

Krupková

Zvick²,

Wuertz‐Kozak³

2017

eCM

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Transient receptor potential channels (TRP channels) are cation selective transmembrane receptors with diverse structures, activation mechanisms and physiological functions. TRP channels act as cellular sensors for a plethora of stimuli, including temperature, membrane voltage, oxidative stress, mechanical stimuli, pH and endogenous as well as exogenous ligands, thereby illustrating their versatility. As such, TRP channels regulate various functions in both excitable and non-excitable cells, mainly by mediating Ca 2+ homeostasis. Dysregulation of TRP channels is implicated in many pathologies, including cardiovascular diseases, muscular dystrophies and hyperalgesia. However, the importance of TRP channel expression, physiological function and regulation in chondrocytes and intervertebral disc (IVD) cells is largely unexplored. Osteoarthritis (OA) and degenerative disc disease (DDD) are chronic age-related disorders that significantly affect the quality of life by causing pain, activity limitation and disability. Furthermore, currently available therapies cannot effectively slow-down or stop progression of these diseases. Both OA and DDD are characterised by reduced tissue cellularity, enhanced inflammatory responses and molecular, structural and mechanical alterations of the extracellular matrix, hence affecting load distribution and reducing joint flexibility. However, knowledge on how chondrocytes and IVD cells sense their microenvironment and respond to its changes is still limited. In this review, we introduced six families of mammalian TRP channels, their mechanisms of activation as well as activation-driven cellular consequences. We summarised the current knowledge on TRP channel expression and activity in chondrocytes and IVD cells and the significance of TRP channels as therapeutic targets for the treatment of OA and DDD.

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Section: Wwwecmjournalorg O Krupkova Et Al Trp Channels In Joint Dmentioning

confidence: 99%

The role of transient receptor potential channels in joint diseases

Krupková

Zvick²,

Wuertz‐Kozak³

2017

eCM

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“…Increased apoptosis was observed in Pkd2 transgenic mice and in Pkd2 knockout renal cells isolated from Pkd2 conditional knockout mice (88,89). Calcium influx mediated by transient receptor potential (TRP) channels in the plasma membrane triggers the cell death (90).…”

Section: Apoptosis In Pkd1 or Pkd2 Mutant Animal Modelsmentioning

confidence: 99%

Apoptosis in Polycystic Kidney Disease: From Pathogenesis to Treatment

Zhou

2015

Polycystic Kidney Disease

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“…Our work also found that loss of PC2 can increase the expression of b-catenin, axin2 and c-Myc. This suggests that PC2 may play a function role in inhibition of β-catenin-dependent Wnt signaling [44]. All of these results indicated that have shown that the loss of Pkd1 and Pkd2 account for abnormal activation of Wnt signaling pathways and cystogenesis.…”

Section: Wnt Pathwaymentioning

confidence: 78%

“…Many signaling pathways control ADPKD cyst formation such as the mammalian target of rapamycin (mTOR) [56,57], cyclic adenosine monophosphate (cAMP) [58,59], Wnt signaling pathway [44,60], G protein coupled receptor [GPCR] [61] and Signal Transducer and Activator of Transcription (STAT) signaling pathway [62] (Figure 1).…”

Section: Signaling Pathways As Targets In Pkd Treatmentmentioning

confidence: 99%

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Present Status and Advances in Autosomal Dominant Polycystic Kidney Disease

Li¹

2017

Cell Mol Med

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Autosomal dominant polycystic kidney disease (ADPKD) is the most common genetic disorder of the kidney. The mainly clinical manifestation is progressive cyst formation in bilateral kidneys, impairs normal renal parenchyma, and ultimately results in end-stage renal disease (ESRD). Extra-renal lesions include cystic liver or pancreas, brain aneurysm and cardiovascular defects. Mutations in either PKD1 or PKD2 genes result in the disease, but the former develops more severe clinical phenotypes than the latter. Currently, ADPKD still challenge vast clinicians on account of lacking effective and less side-effect therapy. Intensive study of molecular mechanism of the disease can establish theoretical basis for potential therapeutic targets and guide clinicians to develop new approaches in treatment of this disease. This review will focus on current advances of ADPKD pathogenesis which may benefit the translational therapy and precision medicine for the disease treatment. liver failure [25,26]. The prevalence of intracranial aneurysms (ICA) among ADPKD patients is about 12% [27]. A family history of intracranial hemorrhage can significantly increase the risk of ICA [28]. Therefore, examination and evaluation of extrarenal organ of ADPKD patients is also very important.At present, there is no safe and effective treatment of ADPKD in clinic. Therefore, understanding the pathogenesis of ADPKD may provide a new therapeutic target for the clinical treatment and lay the foundation for the development of various biological and drug treatments for ADPKD. [30,31]. Polycystin-1 is found in most segments of the nephron and is distributed in a variety of subcellular structures such as the primary cilia, cytoplasmic vesicles, plasma membrane at focal adhesions, desmosomes, adherens junctions, and possibly endoplasmic reticulum and nuclei. Among them, polycystin-1 distributed in primary cilia is considered to play an important role in the mechano/chemo-sensor function [32][33][34], whereas polycystin-1 distributed in the side wall and the basal body participates in the formation of intercellular adhesion and focal adhesion [35]. In addition, a cleavage product of polycystin-1 that includes the C-terminal tail can translocate to the nucleus and regulate gene transcription [36,37]. PKD Genes and Proteins

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Conditional Mutation of Pkd2 Causes Cystogenesis and Upregulates β-Catenin

Cited by 76 publications

References 66 publications

The role of transient receptor potential channels in joint diseases

The role of transient receptor potential channels in joint diseases

Apoptosis in Polycystic Kidney Disease: From Pathogenesis to Treatment

Present Status and Advances in Autosomal Dominant Polycystic Kidney Disease

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