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Tissue-Specific Cell Signaling pp 163–193Cite as

Signaling Pathways Involved in Kidney and Urinary Tract Physiology and Pathology

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Abstract

The kidneys are responsible for maintaining homeostasis, keeping the internal milieu in conditions that sustain life. A number of signaling pathways are implicated in all these feedback loops of regulation, and their disruption or overactivation might contribute to several diseases culminating in kidney failure and may, also, lead to kidney cancer. Because specific signaling cascades are also activated in the various histological subtypes of renal cell carcinoma, type-specific tailoring of targeted therapies is desirable. The urinary tract functions as a conduit that drives urine produced in the kidneys as a means of detoxification, for storage in the bladder and finally excretion by the urethra. This micturition cycle is highly coordinated, with prominent influence from the nervous system and related signaling pathways. Changes in these receptors and mediators disrupt the cycle and produce lower urinary tract symptoms which aggravate patients’ quality of life. Also, the urothelium covering the upper and lower urinary tract is not the same, hence signaling mechanisms involved in bladder and upper tract urothelial carcinoma are necessarily different. In this chapter we present and discuss some of the most relevant signaling cascades involved in kidney and urinary tract physiology and pathology, including non-neoplastic diseases and cancer.

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Abbreviations

α-AR:

Alpha adrenoceptor

AC:

Adenylyl cyclase

Ach:

Acetylcholine

ADPKD:

Autosomal dominant polycystic kidney disease

AKT/PKB:

Protein kinase B

ANP:

Atrial natriuretic peptide

APC:

Adenomatosis polyposis colon

AR:

Androgen receptor

ATP:

Adenosine triphosphate

β-AR:

Beta-adrenoceptors

b-FGF:

Basic fibroblast growth factor

BlCa:

Bladder cancer

BPH:

Benign prostatic hyperplasia

BUC:

Bladder urothelial carcinoma

CAIX:

Carbonic anhydrase IX

cAMP:

Cyclic adenosine monophosphate

ccRCC:

Clear cell renal cell carcinoma

CDH1:

E-cadherin

CDKN2A:

Cyclin-dependent kinase inhibitor 2A

cGMP:

Cyclic guanosine monophosphate

chRCC:

Chromophobe renal cell carcinoma

CK1:

Casein kinase 1

CKD:

Chronic kidney disease

COX:

Cyclooxygenase

CTLA-4:

Cytotoxic T-lymphocyte-associated protein 4

DAG:

Diacylglycerol

DHT:

5α-dihydrotestosterone

DKD:

Diabetic kidney disease

EGF:

Endothelial growth factor

EGFR:

Endothelial growth factor receptor

EMT:

Epithelial-to-mesenchymal transition

EpCAM:

Epithelial cell adhesion molecule

ER:

Estrogen-receptor

ET:

Endothelin

FGF:

Fibroblast growth factor

FGFR3:

Fibroblast growth factor receptor 3

FH:

Fumarate hydratase

FLCN:

Folliculin

FSP1:

Fibroblast-specific protein 1

Fzd:

Frizzled proteins

GLUT1:

Glucose transporter 1

GSK3β:

Glycogen synthase kinase 3β

HAT:

Histone acetyltransferase

HB-EGF:

Heparin-binding EGF-like growth factor

HGF:

Hepatocyte growth factor

Hh:

Hedgehog

HIF:

Hypoxia inducible factors

IGF-I:

Insulin-like growth factor I

IL:

Interleukin

IL-6R:

Interleukin-6 receptor

IP3:

Inositol triphosphate

KCa:

Kidney cancer

LUTS:

Lower urinary tract symptoms

MAPK:

Mitogen activated protein kinase

MET:

Mesenchymal-epithelial transition

MIBC:

Muscle-invasive bladder cancer

MMR:

Mismatch repair

MMP:

Matrix metalloproteinase

MSI:

Microsatellite instability

mTOR:

Mammalian target of rapamycin

mTORC:

Mammalian target of rapamycin complex

MUC1:

Mucin 1

nAChRs:

Nicotinic-type cholinergic receptors

NMIBC:

Non muscle-invasive bladder cancer

NO:

Nitric oxide

PAI-1:

Plasminogen activator inhibitor-1

PDE:

Phosphodiesterase

PDGF:

Platelet derived growth factor

PD-L1:

Programmed death ligand 1

PIP3:

Phosphatidylinositol-3,4,5-triphosphate

PI3K:

Phosphoinositide 3-kinase

PKA:

Protein kinase A

PKC:

Protein kinase C

PKD:

Polycystic kidney disease

PKG:

Protein kinase G

PLC:

Phospholipase C

PPARγ:

Peroxisome proliferator-activated receptor-gamma

pRCC:

Papillary renal cell carcinoma

PTH:

Parathyroid hormone

RCC:

Renal cell carcinoma

ROS:

Reactive oxygen species

SDH:

Succinate dehydrogenase

SIRT:

Sirtuin

STAG2:

Stromal antigen 2

STAT3:

Signal transducer and activator of transcription 3

TAK1:

TGF-β-activated kinase 1

TERT:

Telomerase reverse transcriptase

TGF-β1:

Transforming growth factor beta 1

TRP:

Transmembrane receptor potential

TRPV1:

Transient receptor potential cation channel subfamily V member 1

TSC:

Tuberous sclerosis complex

UTUC:

Upper tract urothelial carcinoma

VEGF:

Vascular endothelial growth factor

VHL:

Von Hippel Lindau

VIP:

Vasoactive intestinal peptide

WHO:

World Health Organization

WIF1:

Wnt inhibitory factor 1

YAP:

Yes-associated protein

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Acknowledgments

JL is supported by an FCT—Fundação para a Ciência e Tecnologia—fellowship (SFRH/BD/132751/2017).

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Authors and Affiliations

  1. Department of Pathology, Portuguese Oncology Institute of Porto (IPO Porto), R. Dr. António Bernardino de Almeida, 4200-072, Porto, Portugal

    João Lobo & Rui Henrique

  2. Cancer Biology and Epigenetics Group, Research Center of Portuguese Oncology Institute of Porto (GEBC CI-IPOP) and Porto Comprehensive Cancer Center (P.CCC), R. Dr. António Bernardino de Almeida, 4200-072, Porto, Portugal

    João Lobo & Rui Henrique

  3. Department of Pathology and Molecular Immunology, Institute of Biomedical Sciences Abel Salazar, University of Porto (ICBAS-UP), Rua Jorge Viterbo Ferreira 228, 4050-513, Porto, Portugal

    João Lobo & Rui Henrique

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Correspondence to Rui Henrique .

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  1. Laboratory of Signal Transduction, Department of Medical Sciences, Institute of Biomedicine—iBiMED, University of Aveiro, Aveiro, Portugal

    Joana Vieira Silva

  2. Laboratory of Protein Phosphorylation and Proteomics, Department of Cellular and Molecular Medicine, Faculty of Medicine, KU Leuven, Leuven, Belgium

    Maria João Freitas

  3. Laboratory of Signal Transduction, Department of Medical Sciences, Institute of Biomedicine—iBiMED, University of Aveiro, Aveiro, Portugal

    Margarida Fardilha

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Lobo, J., Henrique, R. (2020). Signaling Pathways Involved in Kidney and Urinary Tract Physiology and Pathology. In: Silva, J.V., Freitas, M.J., Fardilha, M. (eds) Tissue-Specific Cell Signaling. Springer, Cham. https://doi.org/10.1007/978-3-030-44436-5_6

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