Magda Hamzawy1, Sarah Ali Abdelhameed Gouda1, Laila Rashid2, Mary Attia Morcos3, Heba Shoukry1, Nivin Sharawy4,5. 1. Department of Physiology, Faculty of Medicine, Cairo University, Cairo, Egypt. 2. Department of Biochemistry, Faculty of Medicine, Cairo University, Cairo, Egypt. 3. Department of histology, Faculty of Medicine, Cairo University, Cairo, Egypt. 4. Department of Physiology, Faculty of Medicine, Cairo University, Cairo, Egypt. nivinsharawi@gmail.com. 5. Cairo University Hospitals, Cairo, Egypt. nivinsharawi@gmail.com.
Abstract
BACKGROUND AND AIMS: Apoptosis, autophagy and cell cycle arrest are cellular responses to injury which are supposed to play fundamental roles in initiation and progression of diabetic nephropathy (DN). The aims of the present study is to shed light on the potential effects of vitamin D analog 22-oxacalcitriol (OCT) on different cell responses during DN, and the possible interplay between both glucose, immune system and vitamin D in determining the cell fate. METHOD: All rats were randomly allocated into one of three groups: control, vehicle-treated DN group and OCT-treated DN group. Eight weeks after induction of diabetes, the rats were killed. Fasting blood glucose levels, serum 25 (OH) D, renal functions, cytokines and gene expression of autophagy, apoptotic and cell cycle arrest markers were assessed. In addition, the histological assessment of renal architecture was done. RESULTS: OCT treatment remarkably improved the renal functions and albuminuria. The reductions in mesangial cell hypertrophy, extracellular matrix as well as cell loss were significantly associated with upregulation of pro-autophagy gene expressions and downregulation of both pro-apoptotic and G1-cell cycle arrest genes expression. The reno-protective effects of OCT treatment were associated with significant attenuation of the fasting blood glucose, serum IL-6, renal TLR-4 and IFN-g gene expression. CONCLUSION: Modulator effects of OCT on glucose and immune system play important roles in renal cell fate decision and chronic kidney disease progression.
BACKGROUND AND AIMS: Apoptosis, autophagy and cell cycle arrest are cellular responses to injury which are supposed to play fundamental roles in initiation and progression of diabetic nephropathy (DN). The aims of the present study is to shed light on the potential effects of vitamin D analog 22-oxacalcitriol (OCT) on different cell responses during DN, and the possible interplay between both glucose, immune system and vitamin D in determining the cell fate. METHOD: All rats were randomly allocated into one of three groups: control, vehicle-treated DN group and OCT-treated DN group. Eight weeks after induction of diabetes, the rats were killed. Fasting blood glucose levels, serum 25 (OH) D, renal functions, cytokines and gene expression of autophagy, apoptotic and cell cycle arrest markers were assessed. In addition, the histological assessment of renal architecture was done. RESULTS: OCT treatment remarkably improved the renal functions and albuminuria. The reductions in mesangial cell hypertrophy, extracellular matrix as well as cell loss were significantly associated with upregulation of pro-autophagy gene expressions and downregulation of both pro-apoptotic and G1-cell cycle arrest genes expression. The reno-protective effects of OCT treatment were associated with significant attenuation of the fasting blood glucose, serum IL-6, renal TLR-4 and IFN-g gene expression. CONCLUSION: Modulator effects of OCT on glucose and immune system play important roles in renal cell fate decision and chronic kidney disease progression.
Authors: Martha M Monick; Linda S Powers; Katherine Walters; Nina Lovan; Michael Zhang; Alicia Gerke; Sif Hansdottir; Gary W Hunninghake Journal: J Immunol Date: 2010-10-04 Impact factor: 5.422
Authors: Dairmuid M Moran; M Adrian Mattocks; Paul A Cahill; Leonidas G Koniaris; Iain H McKillop Journal: J Surg Res Date: 2007-06-14 Impact factor: 2.192
Authors: I M Aparicio; J Espino; I Bejarano; A Gallardo-Soler; M L Campo; G M Salido; J A Pariente; F J Peña; J A Tapia Journal: Sci Rep Date: 2016-09-16 Impact factor: 4.379
Authors: Adrian R Martineau; Katalin A Wilkinson; Sandra M Newton; R Andres Floto; Anthony W Norman; Keira Skolimowska; Robert N Davidson; Ole E Sørensen; Beate Kampmann; Christopher J Griffiths; Robert J Wilkinson Journal: J Immunol Date: 2007-06-01 Impact factor: 5.422