Renal Autocrine and Paracrine Signaling: A Story of Self-protection

Leipziger, Jens; Praetorius, Helle A.

doi:10.1152/physrev.00014.2019

Cited by 21 publications

(14 citation statements)

References 758 publications

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“…Typically, the oxygen and substrate demands for reabsorption are autoregulated via the renal blood flow in a complex way unique to the kidney. The regulatory mechanisms include the autocrine, paracrine, and renin-angiotensin hormonal systems (RAS) (reviewed in ref [ 106 ]). In nephrons, NO, as a part of the paracrine system, and angiotensin II antagonistically control glomerular hemodynamic and reabsorptive activities [ 104 ].…”

Section: The Mechanisms Of Kidney Failure Under Conditions Of the Met...mentioning

confidence: 99%

Metabolic Syndrome and β-Oxidation of Long-Chain Fatty Acids in the Brain, Heart, and Kidney Mitochondria

Panov

Mayorov

Dikalov

2022

IJMS

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We present evidence that metabolic syndrome (MetS) represents the postreproductive stage of the human postembryonic ontogenesis. Accordingly, the genes governing this stage experience relatively weak evolutionary selection pressure, thus representing the metabolic phenotype of distant ancestors with β-oxidation of long-chain fatty acids (FAs) as the primary energy source. Mitochondria oxidize at high-rate FAs only when succinate, glutamate, or pyruvate are present. The heart and brain mitochondria work at a wide range of functional loads and possess an intrinsic inhibition of complex II to prevent oxidative stress at periods of low functional activity. Kidney mitochondria constantly work at a high rate and lack inhibition of complex II. We suggest that in people with MetS, oxidative stress is the central mechanism of the heart and brain pathologies. Oxidative stress is a secondary pathogenetic mechanism in the kidney, while the primary mechanisms are kidney hypoxia caused by persistent hyperglycemia and hypertension. Current evidence suggests that most of the nongenetic pathologies associated with MetS originate from the inconsistencies between the metabolic phenotype acquired after the transition to the postreproductive stage and excessive consumption of food rich in carbohydrates and a sedentary lifestyle.

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Section: The Mechanisms Of Kidney Failure Under Conditions Of the Met...mentioning

confidence: 99%

Metabolic Syndrome and β-Oxidation of Long-Chain Fatty Acids in the Brain, Heart, and Kidney Mitochondria

Panov

Mayorov

Dikalov

2022

IJMS

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“…The in vivo kidney microenvironment contains an intricate web of inciting factors (including cytokines and chemokines) that influence a multitude of cellular processes, and this diversity cannot be fully replicated in vitro. Local paracrine signaling is a physiologic process integral to the kidney, fostering a collective and protective renal tissue response to regulate overall kidney function in response to various systemic stimuli [ 72 ]. Additionally, the continued upregulation of STAT1 activation in kidney grafts after CS + Tx at the 9-day post-surgery timepoint lends further support to our earlier hypothesis.…”

Section: Discussionmentioning

confidence: 99%

Cold Storage Followed by Transplantation Induces Interferon-Gamma and STAT-1 in Kidney Grafts

McGraw

Miller

et al. 2023

IJMS

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Cold storage (CS)-mediated inflammation, a reality of donor kidney processing and transplantation, can contribute to organ graft failure. However, the mechanisms by which this inflammation is perpetuated during and after CS remain unclear. Here, we examined the immunoregulatory roles of signal transducer and activator of transcription (STAT) family proteins, most notably STAT1 and STAT3, with our in vivo model of renal CS and transplant. Donor rat kidneys were exposed to 4 h or 18 h of CS, which was then followed by transplantation (CS + transplant). STAT total protein level and activity (phosphorylation) were evaluated via Western blot analysis and mRNA expression was tabulated using quantitative RT-PCR after organ harvest on day 1 or day 9 post-surgery. In vivo assays were further corroborated via similar analyses featuring in vitro models, specifically proximal tubular cells (human and rat) as well as macrophage cells (Raw 264.7). Strikingly, gene expression of IFN-γ (a pro-inflammatory cytokine inducer of STAT) and STAT1 were markedly increased after CS + transplant. STAT3 dephosphorylation was additionally observed after CS, a result suggestive of dysregulation of anti-inflammatory signaling as phosphorylated STAT3 acts as a transcription factor in the nucleus to increase the expression of anti-inflammatory signaling molecules. In vitro, IFN-γ gene expression as well as amplification of downstream STAT1 and inducible nitric oxide synthase (iNOS; a hallmark of ischemia reperfusion injury) was remarkably increased after CS + rewarming. Collectively, these results demonstrate that aberrant induction of STAT1 is sustained in vivo post-CS exposure and post-transplant. Thus, Jak/STAT signaling may be a viable therapeutic target during CS to mitigate poor graft outcomes when transplanting kidneys from deceased donors.

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“…A particularity of several purinergic receptors is their apical localization in epithelial cells ( 4 ). ATP release is activated by mechanical stimulation such as cell swelling and shear stress, and ATP together with its hydrolysis product adenosine are part of local intrarenal mechanisms that help regulate glomerular filtration rate (GFR) ( 64 , 65 ), and water and electrolyte transport in collecting duct principal cells ( 33 , 66 ). Renal disease is often associated with acidosis and intra-renal adenosine has a protective effect following kidney injury ( 43 , 67 – 69 ).…”

Section: Physiological and Pathophysiological Roles Of Purinergic Rec...mentioning

confidence: 99%

Purinergic signaling in the male reproductive tract

et al. 2022

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Purinergic receptors are ubiquitously expressed throughout the body and they participate in the autocrine and paracrine regulation of cell function during normal physiological and pathophysiological conditions. Extracellular nucleotides activate several types of plasma membrane purinergic receptors that form three distinct families: P1 receptors are activated by adenosine, P2X receptors are activated by ATP, and P2Y receptors are activated by nucleotides including ATP, ADP, UTP, UDP, and UDP-glucose. These specific pharmacological fingerprints and the distinct intracellular signaling pathways they trigger govern a large variety of cellular responses in an organ-specific manner. As such, purinergic signaling regulates several physiological cell functions, including cell proliferation, differentiation and death, smooth muscle contraction, vasodilatation, and transepithelial transport of water, solute, and protons, as well as pathological pathways such as inflammation. While purinergic signaling was first discovered more than 90 years ago, we are just starting to understand how deleterious signals mediated through purinergic receptors may be involved in male infertility. A large fraction of male infertility remains unexplained illustrating our poor understanding of male reproductive health. Purinergic signaling plays a variety of physiological and pathophysiological roles in the male reproductive system, but our knowledge in this context remains limited. This review focuses on the distribution of purinergic receptors in the testis, epididymis, and vas deferens, and their role in the establishment and maintenance of male fertility.

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Renal Autocrine and Paracrine Signaling: A Story of Self-protection

Cited by 21 publications

References 758 publications

Metabolic Syndrome and β-Oxidation of Long-Chain Fatty Acids in the Brain, Heart, and Kidney Mitochondria

Metabolic Syndrome and β-Oxidation of Long-Chain Fatty Acids in the Brain, Heart, and Kidney Mitochondria

Cold Storage Followed by Transplantation Induces Interferon-Gamma and STAT-1 in Kidney Grafts

Purinergic signaling in the male reproductive tract

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