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Article

Possible Underlying Mechanisms for the Renoprotective Effect of Retinoic Acid-Pretreated Wharton’s Jelly Mesenchymal Stem Cells against Renal Ischemia/Reperfusion Injury

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Department of Biochemistry, Faculty of Veterinary Medicine, Mansoura University, Mansoura 35516, Egypt
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Institute of Global Public Health and Human Ecology, School of Science and Engineering, American University, Cairo 11835, Egypt
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Department of Medical Physiology, Faculty of Medicine, Mansoura University, Mansoura 35516, Egypt
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Urology and Nephrology Center, Mansoura University, Mansoura 35516, Egypt
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Department of Biochemistry, Faculty of Medicine, Mansoura University, Mansoura 35516, Egypt
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Department of Anatomy and Embryology, Faculty of Medicine, Mansoura University, Mansoura 35516, Egypt
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Physiological Sciences Department, Fakeeh College for Medical Sciences, Jeddah 21461, Saudi Arabia
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Department of Basic Medical Sciences, College of Medicine, AlMaarefa University, Riyadh 71666, Saudi Arabia
*
Author to whom correspondence should be addressed.
Academic Editor: Masaru Katoh
Cells 2022, 11(13), 1997; https://doi.org/10.3390/cells11131997
Received: 6 June 2022 / Revised: 18 June 2022 / Accepted: 20 June 2022 / Published: 22 June 2022
(This article belongs to the Special Issue Wnt Signaling in Health and Diseases 2022)
Objectives: The current work investigated the effect of Wharton jelly mesenchymal stem cells (WJ-MSCs) pretreated with all-trans-retinoic acid (ATRA) on renal ischemia in rats and the possible role of oxidative stress, apoptotic and Wnt/β-Catenin signaling pathways, and inflammatory cytokines in their effects. Methods: The study included 90 male Sprague Dawley rats that were allocated to five groups (n = 18 rats): (I) Sham-operated group (right nephrectomy was performed); (II) Ischemia/reperfusion injury (IRI) group, a sham group with 45-min renal ischemia on the left kidney; (III) ATRA group, an ischemic group with an intravenous (i.v.) administration of ATRA 10 µM, 10 min post-surgery); (IV) WJ-MSCs group, an IRI group with an i.v. administration of 150 µL containing 7 × 106 WJ-MSCs, 10 min post-surgery; (V) WJ-MSCs + ATRA group, an IRI group with an i.v. administration of 150 µL of 7 × 106 WJ-MSCs pretreated with 10 µM ATRA. At the end of the experiments, serum creatinine, BUN micro-albuminuria (MAU), urinary protein, markers of redox state in the left kidney (MDA, CAT, SOD, and GSH), and the expression of Bax, IL-6, HIF-1α, Wnt7B, and β-catenin genes at the level of mRNA as well as for immunohistochemistry for NFkB and β-Catenin markers were analyzed. Results: The current study found that 45-min of renal ischemia resulted in significant impairment of kidney function (evidenced by the increase in serum creatinine, BUN, and urinary proteins) and deterioration of the kidney morphology, which was associated with a significant increase in redox state (evidenced by an increase in MDA and a decrease in GSH, SOD, and CAT), and a significant increase in inflammatory and apoptotic processes (evidenced by an increase in Bax and IL-6, NFkB, Wnt7B, β-catenin and HIF-1α) in kidney tissues (p < 0.05). On the other hand, treatment with ATRA, WJ-MSCs, or a combination of both, caused significant improvement in kidney function and morphology, which was associated with significant attenuation of oxidative stress, apoptotic markers, and inflammatory cytokines (IL6 and NFkB) with the upregulation of HIF-1α and β-catenin in kidney tissues (p < 0.05). Moreover, the renoprotective effect of WJ-MSCs pretreated with ATRA was more potent than WJ-MSCs alone. Conclusions: It is concluded that preconditioning of WJ-MSCs with ATRA may enhance their renoprotective effect. This effect could be due to the upregulation of the beta-catenin/Wnt pathway and attenuation of apoptosis, inflammation, and oxidative stress. View Full-Text
Keywords: retinoic acid; WJ-MSCs; Wnt/β-catenin; renal ischemia retinoic acid; WJ-MSCs; Wnt/β-catenin; renal ischemia
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MDPI and ACS Style

Barakat, M.; Hussein, A.M.; Salama, M.F.; Awadalla, A.; Barakat, N.; Serria, M.; El-Shafey, M.; El-Sherbiny, M.; El Adl, M.A. Possible Underlying Mechanisms for the Renoprotective Effect of Retinoic Acid-Pretreated Wharton’s Jelly Mesenchymal Stem Cells against Renal Ischemia/Reperfusion Injury. Cells 2022, 11, 1997. https://doi.org/10.3390/cells11131997

AMA Style

Barakat M, Hussein AM, Salama MF, Awadalla A, Barakat N, Serria M, El-Shafey M, El-Sherbiny M, El Adl MA. Possible Underlying Mechanisms for the Renoprotective Effect of Retinoic Acid-Pretreated Wharton’s Jelly Mesenchymal Stem Cells against Renal Ischemia/Reperfusion Injury. Cells. 2022; 11(13):1997. https://doi.org/10.3390/cells11131997

Chicago/Turabian Style

Barakat, Mai, Abdelaziz M. Hussein, Mohamed F. Salama, Amira Awadalla, Nashwa Barakat, Mohamed Serria, Mohamed El-Shafey, Mohamed El-Sherbiny, and Mohamed A. El Adl. 2022. "Possible Underlying Mechanisms for the Renoprotective Effect of Retinoic Acid-Pretreated Wharton’s Jelly Mesenchymal Stem Cells against Renal Ischemia/Reperfusion Injury" Cells 11, no. 13: 1997. https://doi.org/10.3390/cells11131997

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