Naringenin induces laxative effects by upregulating the expression levels of c-Kit and SCF, as well as those of aquaporin 3 in mice with loperamide-induced constipation

Constipation is characterized by reduced number of bowel movements, dry stools, and difficult defecation. Yangyin Tongmi capsule (YTC), a traditional Chinese formula, is used in the treatment of constipation, while the underlying mechanisms remain unknown. Herein, this work attempted to prove the effects of YTC on constipation treatment and its possible mechanisms. KM mice were randomly divided into four groups (n = 10/group) and treated with double distilled water (Control), diphenoxylate (Model: 10 mg/kg), or diphenoxylate plus low-dose YTC (L-YTC: 0.6 g/kg) or high-dose YTC (H-YTC: 1.2 g/kg). The data indicated that YTC can significantly shorten the discharge time of the first black stool, improve intestinal propulsion rate, and increase the water content and quantity of feces in mice. ELISA suggested that YTC regulate the content of intestinal hormones and neurotransmitters, such as motilin (MTL), gastrin (GT), somatostatin (SST), substance P (SP), acetylcholine (Ach), and nitric oxide (NO). The expression levels of aquaporin 3 (AQP3) and aquaporin 8 (AQP8) in the colon were examined by immunohistochemistry. In the meantime, the expression levels of P2X2, C-kit, and stem cell factor (SCF) in the colon were examined by western blot analysis. The results of this study suggest that YTC has mitigative effects on diphenoxylate-induced constipation by regulating the content of intestinal hormones and neurotransmitters and regulating the expression of related proteins in the colon.

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Cortisol regulates eel (Anguilla anguilla) aquaporin 3 (AQP3) mRNA expression levels in gill

General and Comparative Endocrinology ◽

10.1016/j.ygcen.2007.01.031 ◽

2007 ◽

Vol 152 (2-3) ◽

pp. 310-313 ◽

Cited By ~ 14

Author(s):

C.P. Cutler ◽

C. Phillips ◽

N. Hazon ◽

G. Cramb

Keyword(s):

Mrna Expression ◽

Anguilla Anguilla ◽

Aquaporin 3 ◽

Expression Levels ◽

Mrna Expression Levels

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Molecular Characterization of Aquaporin 1 and Aquaporin 3 from the Gills of the African Lungfish, Protopterus annectens, and Changes in Their Branchial mRNA Expression Levels and Protein Abundance during Three Phases of Aestivation

Frontiers in Physiology ◽

10.3389/fphys.2016.00532 ◽

2016 ◽

Vol 7 ◽

Cited By ~ 5

Author(s):

You R. Chng ◽

Jasmine L. Y. Ong ◽

Biyun Ching ◽

Xiu L. Chen ◽

Kum C. Hiong ◽

...

Keyword(s):

Mrna Expression ◽

Molecular Characterization ◽

Protein Abundance ◽

Aquaporin 3 ◽

Expression Levels ◽

Aquaporin 1 ◽

Protopterus Annectens ◽

African Lungfish ◽

Mrna Expression Levels

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Study of the Mechanism Underlying the Onset of Diabetic Xeroderma Focusing on an Aquaporin-3 in a Streptozotocin-Induced Diabetic Mouse Model

International Journal of Molecular Sciences ◽

10.3390/ijms20153782 ◽

2019 ◽

Vol 20 (15) ◽

pp. 3782 ◽

Cited By ~ 3

Author(s):

Nobutomo Ikarashi ◽

Nanaho Mizukami ◽

Risako Kon ◽

Miho Kaneko ◽

Ryogo Uchino ◽

...

Keyword(s):

Blood Glucose ◽

Water Transport ◽

Diabetic Mouse ◽

Diabetic Patients ◽

Diabetic Mice ◽

Aquaporin 3 ◽

Expression Levels ◽

Glucose Levels ◽

Blood Glucose Levels ◽

Site Binding

Xeroderma is a frequent complication in diabetic patients. In this study, we investigated the mechanism underlying the onset of diabetic xeroderma, focusing on aquaporin-3 (AQP3), which plays an important role in water transport in the skin. Dermal water content in diabetic mice was significantly lower than that in control mice. The expression level of AQP3 in the skin was significantly lower in diabetic mice than in control mice. One week after streptozotocin (STZ) treatment, despite their increased blood glucose levels, mice showed no changes in the expression levels of AQP3, Bmal1, Clock, and D site-binding protein (Dbp) in the skin and 8-hydroxydeoxyguanosine (8-OHdG) in the urine. In contrast, two weeks after STZ treatment, mice showed increases in the blood glucose level, decreases in AQP3, Bmal1, Clock, and Dbp levels, and increases in the urinary levels of 8-OHdG. The results of this study suggest that skin AQP3 expression decreases in diabetes, which may limit water transport from the vessel side to the corneum side, causing dry skin. In addition, in diabetic mice, increased oxidative stress triggered decreases in the expression levels of Bmal1 and Clock in the skin, thereby inhibiting the transcription of Aqp3 by Dbp, which resulted in decreased AQP3 expression.

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Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor Erlotinib Induces Dry Skin via Decreased in Aquaporin-3 Expression

Biomolecules ◽

10.3390/biom10040545 ◽

2020 ◽

Vol 10 (4) ◽

pp. 545 ◽

Cited By ~ 2

Author(s):

Nobutomo Ikarashi ◽

Miho Kaneko ◽

Tomofumi Watanabe ◽

Risako Kon ◽

Makana Yoshino ◽

...

Keyword(s):

Epidermal Growth Factor Receptor ◽

Growth Factor ◽

Epidermal Growth Factor ◽

Receptor Tyrosine Kinase ◽

Growth Factor Receptor ◽

Hacat Cells ◽

Dry Skin ◽

Aquaporin 3 ◽

Expression Levels ◽

Epidermal Growth

An adverse reaction of dry skin occurs frequently during treatment with anticancer epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs). In this study, we conducted basic research to clarify the mechanism of EGFR-TKI-induced dry skin and propose new treatments or preventative measures. Dermal water content was significantly lower in the erlotinib-treated mice than in the control group. An assessment of the expression levels of functional genes in the skin revealed that only the expression of the water channel aquaporin-3 (AQP3) was significantly decreased in the erlotinib-treated group. When erlotinib was added to epidermal keratinocyte HaCaT cells, the expression levels of both AQP3 mRNA and protein decreased. Erlotinib treatment also significantly decreased the expression levels of phospho-EGFR and phospho-extracellular signal-regulated kinase (ERK), both in HaCaT cells and mouse skin. Dry skin due to erlotinib may be caused by the decreased expression of AQP3 in the skin, thereby limiting water transport from the vascular side to the corneum side. The decrease in AQP3 may also be attributable to ERK suppression via inhibition of EGFR activity by erlotinib. Therefore, substances that increase AQP3 expression may be effective for erlotinib-induced dry skin.

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Long-term regulation of four renal aquaporins in rats

AJP Renal Physiology ◽

10.1152/ajprenal.1996.271.2.f414 ◽

1996 ◽

Vol 271 (2) ◽

pp. F414-F422 ◽

Cited By ~ 133

Author(s):

J. Terris ◽

C. A. Ecelbarger ◽

S. Nielsen ◽

M. A. Knepper

Keyword(s):

Aquaporin 4 ◽

Osmotic Gradient ◽

Brattleboro Rats ◽

Sprague Dawley ◽

Aquaporin 3 ◽

Expression Levels ◽

Aquaporin 1 ◽

Aquaporin 2 ◽

Sprague Dawley Rats

The aquaporins are molecular water channels expressed in the kidney and other organs. To investigate long-term regulation of renal expression of these water channels, we carried out immunoblotting studies using membrane fractions from rat renal cortex and medulla. Both 48-h water restriction in Sprague-Dawley rats and 5-day arginine vasopressin (AVP) infusion in Brattleboro rats caused significant increases in the expression levels of two aquaporins, aquaporin-2 and aquaporin-3, while the levels of aquaporin-1 and aquaporin-4 were unchanged. The increases in aquaporin-2 and aquaporin-3 expression were seen in inner and outer medulla as well as cortex. Ablation of the corticomedullary interstitial osmotic gradient with an infusion of furosemide did not eliminate the upregulatory response to AVP infusion in Brattleboro rats. Furthermore, 5-day furosemide infusion to Sprague-Dawley rats did not decrease expression levels of the collecting duct aquaporins, but rather increased them. We conclude that the expression of aquaporin-2 and aquaporin-3, but not aquaporin-1 or aquaporin-4, is increased in response to elevated circulating AVP. Because regulation of aquaporin-2 and aquaporin-3 levels was observed in the cortex and because osmotic gradient ablation did not abrogate the increase, we conclude that changes in interstitial osmolality are not necessary for the AVP-induced upregulation of aquaporin-2 and aquaporin-3 expression.

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