Protective Effect of PACAP on Ischemia/Reperfusion-Induced Kidney Injury of Male and Female Rats: Gender Differences

László, Eszter; Juhász, Tamás; Varga, Ádám; Czibere, Bernadett; Kovács, Krisztina; Degrell, Péter; Horváth, Gabriella; Jancsó, Gábor; Stella, Péter; Tamás, Andrea; Reglődi, Dóra

doi:10.1007/s12031-018-1207-y

Cited by 15 publications

(17 citation statements)

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“…The most dramatic amyloid deposition was found in the kidneys of aging PACAP knockout mice, where 100% of the animals developed a severe glomerular infiltration causing functional failure (Gronewold et al, 2017;Reglodi et al, 2018c). In addition, PACAP has a nephroprotective role in various kidney pathologies, such as toxic nephropathies and ischemia/reperfusion-induced kidney injury of rats (Horvath et al, 2019;Laszlo et al, 2019). Binding to its receptors, PACAP initiates the activation of various signaling pathways via the activation of intracellular messengers such as adenylate cyclase, which triggers protein kinase A (PKA), and subsequent activation of the phosphorylate transcription factors such as CREB and mediates different gene expressions (Kienlen Campard et al, 1997;Juhasz et al, 2014b;Dong Q. et al, 2019).…”

Section: Introductionmentioning

confidence: 99%

“…Binding to its receptors, PACAP initiates the activation of various signaling pathways via the activation of intracellular messengers such as adenylate cyclase, which triggers protein kinase A (PKA), and subsequent activation of the phosphorylate transcription factors such as CREB and mediates different gene expressions (Kienlen Campard et al, 1997;Juhasz et al, 2014b;Dong Q. et al, 2019). PACAP has a modulatory role in several signaling cascades such as Notch and sonic hedgehog signaling (Sandor et al, 2014;Fulop et al, 2019), Sox transcription factor activation (Szegeczki et al, 2019), and has an important balancing function in bone morphogenetic protein (BMP) signaling (Jozsa et al, 2019;Laszlo et al, 2019).…”

Section: Introductionmentioning

confidence: 99%

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Physical Activity Protects the Pathological Alterations of Alzheimer’s Disease Kidneys via the Activation of PACAP and BMP Signaling Pathways

Perényi

Szegeczki

Horváth

et al. 2020

Front. Cell. Neurosci.

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Alzheimer's disease (AD) is a neurodegenerative disorder with typical amyloid beta (Aβ) aggregations. Elimination of the Aβ precursors via the kidneys makes the organ a potential factor in the systemic degeneration leading to AD. Pituitary adenylate cyclase-activating polypeptide (PACAP) exerts neuroprotective effects in AD and plays a protective role in kidney pathologies. Increased physical activity is preventive of the formation of AD, but its detailed mechanism and possible connections with PACAP have not been clarified. In the kidneys of AD mice, the effects of physical activity were investigated by comparing wild-type and AD organs. Aβ plaque formation was reduced in AD kidneys after increased training (TAD). Mechanotransduction elevated PACAP receptor expression in TAD mice and normalized the protein kinase A (PKA)-mediated pathways. BMP4/BMPR1 elevation activated Smad1 expression and normalized collagen type IV in TAD animals. In conclusion, our data suggest that elevated physical activity can prevent the AD-induced pathological changes in the kidneys via, at least in part, the activation of PACAP-BMP signaling crosstalk.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Physical Activity Protects the Pathological Alterations of Alzheimer’s Disease Kidneys via the Activation of PACAP and BMP Signaling Pathways

Perényi

Szegeczki

Horváth

et al. 2020

Front. Cell. Neurosci.

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“…In line, PACAP treatment could ameliorate histopathological sequelae in both lungs and kidneys of T. gondii infected mice suffering from acute ileitis [ 12 ], whereas lower pulmonal IFN-γ concentrations were assessed in ex vivo biopsies derived from PACAP versus mock-treated mice with subacute ileitis [ 13 ]. Furthermore, PACAP treatment resulted in pronounced cell protective effects in several models of renal injury [ 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 ], which also held true for acute endotoxin-induced inflammation of the lung [ 52 ]. Due to their potent broncho-relaxant as well as anti-inflammatory modes of actions, synthetic PACAP analogues have been approved as therapeutic options against bronchial asthma [ 52 , 53 ].…”

Section: Discussionmentioning

confidence: 99%

Pituitary Adenylate Cyclase-Activating Polypeptide Alleviates Intestinal, Extra-Intestinal and Systemic Inflammatory Responses during Acute Campylobacter jejuni-induced Enterocolitis in Mice

et al. 2020

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Human Campylobacter jejuni infections are emerging, and constitute a significant health burden worldwide. The ubiquitously expressed pituitary adenylate cyclase-activating polypeptide (PACAP) is well-known for its cell-protective and immunomodulatory effects. In our actual intervention study, we used an acute campylobacteriosis model and assessed the potential disease-alleviating effects of exogenous PACAP. Therefore, secondary abiotic IL-10−/− mice were perorally infected with C. jejuni and treated with synthetic PACAP38 intraperitoneally from day 2 until day 5 post-infection. Whereas PACAP did not interfere with the gastrointestinal colonization of the pathogen, mice from the PACAP group exhibited less severe clinical signs of C. jejuni-induced disease, as compared to mock controls, which were paralleled by alleviated apoptotic, but enhanced cell proliferative responses in colonic epithelia on day 6 post-infection. Furthermore, PACAP dampened the accumulation of macrophages and monocytes, but enhanced regulatory T cell responses in the colon, which were accompanied by less IFN-γ secretion in intestinal compartments in PACAP versus mock-treated mice. Remarkably, the inflammation-dampening properties of PACAP could also be observed in extra-intestinal organs, and strikingly, even the systemic circulation on day 6 post-infection. For the first time, we provide evidence that synthetic PACAP might be a promising candidate to combat acute campylobacteriosis and post-infectious sequelae.

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“…As BMPs are important indicators of callus formation, we focused on the expression of BMP2, 4, and 6, which have important functions in bone remodeling processes (Li et al 2015;Das et al 2016). BMPs have been shown to have direct connections with PACAP signaling (Laszlo et al 2019). and Smad1.…”

Section: Discussionmentioning

confidence: 99%

Lack of Pituitary Adenylate Cyclase–Activating Polypeptide (PACAP) Disturbs Callus Formation

et al. 2019

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Pituitary adenylate cyclase-activating polypeptide (PACAP) is a naturally secreted signaling peptide and has important regulatory roles in the differentiation of the central nervous system and its absence results in disorders in femur development. PACAP has an important function in prevention of oxidative stress or mechanical stress in chondrogenesis but little is known about its function in bone regeneration. A new callus formation model was set to investigate its role in bone remodeling. Fracturing was 5 mm distal from the proximal articular surface of the tibia and the depth was 0.5 mm. Reproducibility of callus formation was investigated with CT 3, 7, and 21 days after the operation. Absence of PACAP did not alter the alkaline phosphatase (ALP) activation in PACAP KO healing process. In developing callus, the expression of collagen type I increased in wild-type (WT) and PACAP KO mice decreased to the end of healing process. Expression of the elements of BMP signaling was disturbed in the callus formation of PACAP KO mice, as bone morphogenic protein 4 (BMP4) and 6 showed an early reduction in bone regeneration. However, elevated Smad1 expression was demonstrated in PACAP KO mice. Our results indicate that PACAP KO mice show various signs of disturbed bone healing and suggest PACAP compensatory and fine tuning effects in proper bone regeneration.

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Protective Effect of PACAP on Ischemia/Reperfusion-Induced Kidney Injury of Male and Female Rats: Gender Differences

Cited by 15 publications

References 50 publications

Physical Activity Protects the Pathological Alterations of Alzheimer’s Disease Kidneys via the Activation of PACAP and BMP Signaling Pathways

Physical Activity Protects the Pathological Alterations of Alzheimer’s Disease Kidneys via the Activation of PACAP and BMP Signaling Pathways

Pituitary Adenylate Cyclase-Activating Polypeptide Alleviates Intestinal, Extra-Intestinal and Systemic Inflammatory Responses during Acute Campylobacter jejuni-induced Enterocolitis in Mice

Lack of Pituitary Adenylate Cyclase–Activating Polypeptide (PACAP) Disturbs Callus Formation

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