Effect of 1,25-dihydroxyvitamin D3 delaying renal interstitial fibrosis by T regulatory cell
GAO Feng1 GUO Hui2
1.The Second Clinical Medical College, Shanxi Medical University, Shanxi Province, Taiyuan 030001, China;
2.Department of Nephrology, the Second Hospital of Shanxi Medical University, Shanxi Province, Taiyuan 030001, China
Abstract：Objective To study the effect of 1, 25-dihydroxyvitamin D3 [1,25(OH)2D3] on renal interstitial fibrosis in rats with unilateral ureteral obstruction (UUO). Methods According to random number table method, 54 wistar rats were divided into sham operation group (group A), UUO group (group B) and 1,25 (OH)2D3 treatment group (group C), with 18 rats in each group. Group C was gavaged 3 ng/(d·100 g) of 1,25（OH）2D3 every day. Group A and group B were gavaged the same amount of peanut oil. The left ureter ligation was performed in group B and group C. Group A was treated with ureteral free, but not ligated. On the 1st, 3rd and 7th day after operation, 6 rats were killed in batches, and the left kidney was retained. Serum creatinine were measured in each group. Renal pathological changes were observed by hematoxylin-eosin (HE) staining. The expression of a-smooth muscle actin (a-SMA) and forkhead P3 protein (FOXP3) in the kidney was detected by immunohistochemistry. Western blot was used to detect the protein expression of phosphorylated adenosine monophosphate activated protein kinase (p-AMPK). Results On the 1st, 3rd and 7th day after operation, the serum creatinine，a-SMA levels of group B was higher than those of group A, and the serum creatinine，a-SMA levels of group C was lower than those of group B (all P < 0.05). The renal tissue morphology of group A was normal, while the renal tissue of group B was prolonged with the obstruction time, showing renal tubules dilatation and interstitial edema, while the tubular degeneration of group C was reduced compared with that of group B. On the 1st, 3rd and 7th day after operation, p-AMPK and FOXP3 levels in group B were lower than those in group A, p-AMPK and FOXP3 levels in group C were higher than those in group B (all P < 0.05). Conclusion 1,25(OH)2D3 can delay renal interstitial fibrosis, and its mechanism may be related to the activation of AMPK to promote the activation of regulatory T cells.
[1] Zhang B，Shi YQ，Zou JJ，et al. High glucose stimulates cell proliferation and Collagen Ⅳ production in rat mesangial cells through inhibiting AMPK-KATP signaling [J]. Int Urol Nephrol，2017，49（11）：2079-2086.
[2] Lee MJ，Feliers D，Mariappan MM，et al. A role for AMP-activated protein kinase in diabetes-induced renal hypertrophy [J]. Am J Physiol Renal Physiol，2007，292（2）：F617-F627.
[3] Peter T，Hawley SA，Clarke RG，et al. Regulation of the energy sensor AMP-activated protein kinase by antigen receptor and Ca2+ in T lymphocytes [J]. J Exp Med，2006， 203（7）：1665-1670.
[4] Duan W，Ding Y，Yu X，et al. Metformin mitigates autoimmune insulitis by inhibiting Th1 and Th17 responses while promoting Treg production [J]. Am J Transl Res，2019， 11（4）：2393-2402.
[5] MahajanD，Wang Y，Qin X，et al. CD4+CD25+ Regulatory T Cells Protect against Injury in an Innate Murine Model of Chronic Kidney Disease [J]. J Am Soc of Nephrol，2006， 17（10）：2731-2741.
[6] Chung S，Kim S，Kim M，et al. Treatment combining aliskiren with paricalcitol is effective against progressive renal tubulointerstitial fibrosis via dual blockade of intrarenal renin [J]. PLoS One，2017，12（7）：e0181757.
[7] Djudjaj S，Martin IV，Buhl EM，et al. Macrophage Migration Inhibitory Factor Limits Renal Inflammation and Fibrosis by Counteracting Tubular Cell Cycle Arrest [J]. J Am Soc Nephrol，2017，28（12）：3590-3604.
[8] Liu BC，Tang TT，Lv LL，et al. Renal tubule injury：a driving force toward chronic kidney disease [J]. Kidney Int，2018，93（3）：568-579.
[9] Epstein FH，Blobe GC，Schiemann WP，et al. Role of Transforming Growth Factor （beta） in Human Disease [J]. N Enql J Med，2000，342（18）：1350-1358.
[10] 牛潼，刘琦然，李玲，等.Wnt/β-catenin信号通路对肾小管上皮间充质转分化的调控[J].中华实用儿科临床杂志，2016，31（12）：958-960.
[11] 陈红淑，杨元宵，周小杰，等.肾气丸通过TGF-β1/Smads/ILK信号途径干预肾小管上皮细胞间充质转分化的分子机制[J].中华中医药杂志，2016，31（6）：2102-2105.
[12] 刘慧铭，王圆圆，郭兵.腺苷酸活化蛋白激酶在肾脏纤维化中的研究进展[J].中国当代医药，2018，25（26）：33-36.
[13] Hardie DG. AMP-activated/SNF1 protein kinases：conserved guardians of cellular energy [J]. Nat Rev Mol Cell Biol，2007，8（10）：774-785.
[14] Lu J，Shi J，Li M，et al. Activation of AMPK by metformin inhibits TGF-β-induced collagen production in mouse renal fibroblasts [J]. Life Sci，2015，127：59-65.
[15] Bakhshalizadeh S，Amidi F，Shirazi R，et al. Vitamin D3 regulates steroidogenesis in granulosa cells through AMP-activated protein kinase（AMPK）activation in a mouse model of polycystic ovary syndrome [J]. Cell Biochem Funct，2018，36（4）：183-193.
[16] 王茜，罗静，郭珲.1，25-二羟维生素D3对肾间质纤维化大鼠IL-17的调节作用[J].临床医药实践，2017，26（4）：289-292.
[17] Michalek RD，Gerriets VA，Jacobs SR，et al. Cutting Edge：Distinct Glycolytic and Lipid Oxidative Metabolic Programs Are Essential for Effector and Regulatory CD4+ T Cell Subsets [J]. J Immunol，2011，186（6）：3299-3303.
[18] Gwinn DM，Shackelford DB，Egan DF，et al. AMPK phosphorylation of raptor mediates a metabolic checkpoint [J]. Mol Cell，2008，30（2）：214-226.
[19] Ma EH，Poffenberger MC，Wong AH，et al. The role of AMPK in T cell metabolism and function [J]. Curr Opin Immunol，2017，46：45-52.
[20] Tian Y，Chen T，Wu Y，et al. Pioglitazone stabilizes atherosclerotic plaque by regulating the Th17/Treg balance in AMPK-dependent mechanisma [J]. Cardiovasc Diabetol，2017，16（1）：140.
2020, Vol. 17 
京公网安备 11010502046598号