Objective: To investigate the effects of human umbilical cord mesenchymal stem cells on renal tissue injury and expression of uromodulin in rats with diabetic nephropathy. Methods: The diabetic nephropathy model was established and divided into normal control group (NC group), diabetic kidney disease (DKD) group (DKD group), and human umbilical cord mesenchymal stem cells (HU-MSCs) treatment of diabetic nephropathy group (HU-MSCs+DKD group). The expression of uromodulin (UMOD) and related factors in renal tissue and urine of diabetic nephropathy rats before and after HU-MSCs treatment was detected. Results: In the early stage of renal injury in DKD group, the level of UMOD in urine and renal interstitium increased (P<0.001), and the expression of distal tubule marker protein SLC12a3 decreased. Compared with the control group, HU-MSCs treatment significantly reduced serum urea nitrogen (P<0.01), 24-hour urinary protein (P<0.05), and urinary albumin / creatinine ratio (P<0.05) in DKD rats. After HU-MSCs treatment, glomerular volume decreased, mesangial cells and basement membrane thickening decreased, renal tubular injury decreased, urine and renal interstitial UMOD expression decreased, and SLC12a3 level increased. Conclusion: In the early stage of diabetic nephropathy, HU-MSCs can reduce renal tissue injury, and its reduction of renal tubular injury is related to the decrease of uromodulin in renal tissue.
ZHAO Junhong
,
MI Yan
,
WANG Caili
,
LYU Li
. Effect of human umbilical cord mesenchymal stem cells on the expression of uromodulin in kidney tissues of rats with diabetic nephropathy[J]. Journal of Baotou Medical College, 2025
, 41(5)
: 37
-41
.
DOI: 10.16833/j.cnki.jbmc.2025.05.007
[1] Lin E, Erickson KF. Payer mix among patients receiving dialysis[J]. JAMA, 2020, 324(9): 900-901.
[2] Matoba K, Takeda Y, Nagai Y, et al. Unraveling the role of inflammation in the pathogenesis of diabetic kidney disease[J]. Int J Mol Sci, 2019, 20(14):3393.
[3] Kipp A, Olinger E. What does uromodulin do?[J]. Clin J Am Soc Nephrol, 2020, 16(1): 150-153.
[4] Micanovic R, Khan S, Janosevic D, et al. Tamm-Horsfall Protein RegulatesMononuclear Phagocytes in the Kidney [J]. J Am Soc Nephrol, 2018, 29(3): 841-856.
[5] 修贤杰, 张萍, 郑小鹏, 等. 注射STZ方式对制备糖尿病肾病模型的影响研究[J]. 广东化工, 2020, 47(8): 59-60.
[6] Scheurlen KM, Billeter AT, Kopf S, et al. Serum uromodulin and rouxeny gastric bypass: improvement of a marker reflecting nephron mass[J]. Surg Obes Relat Dis, 2019, 15(8): 1319-1325.
[7] Then C, Then HL, Lechner A, et al. Serum uromodulin and risk for cardiovascular morbidity and mortality in the community-based KORA F4 study[J]. Atherosclerosis, 2020, 297: 1-7.
[8] Micanovic R, Lafavers K, Garimella PS, et al. Uromodulin (tamm-horsfall protein): guardian of urinary and systemic homeostasis[J]. Nephrol Dial Transplant, 2020, 35(1): 33-43.
[9] Bullen AL, Katz R, Lee AK, et al. The sprint trial suggests that markers of tubule cell function in the urine associate with risk of subsequent acute kidney injury while injury markers elevate after the injury[J]. Kidney Int, 2019, 96(2): 470-479.
[10] Wuttke M, Li Y, Li M et al. A catalog of genetic loci asso-ciated with kidney function from analyses of a million individuals[J]. Nat Genet 2019, 51: 957-972.
[11] Schaeffer C, Devuyst O, Rampoldi L, et al. Uromodulin: Roles in health and disease[J]. Annu Rev Physiol. 2021, 83: 477-501.
[12] Ponte B, Sadler MC, Olinger E, et al. Mendelian randomization to assess causality between uromodulin, blood pressure and chronic kidney disease[J]. Kidney Int, 2021, 100(6): 1282-1291.
[13] Pfleiderer S, Zimmerhackl LB, Kinne R, et al. Renal proximal and distal tubular function is attenuated in diabetes mellitus type 1 as determined by the renal excretion of alpha 1-microglobulin and Tamm-Horsfall protein[J]. Clin Investig, 1993, 71(12): 972-977.
[14] Zimmerhackl LB, Pfleiderer S, Kinne R, et al. Tamm-Horsfall-Protein excretion as a marker of ascending limb transport indicates early renal tubular damage in diabetes mellitus type I[J]. Diabet Complications, 1991, 5(2-3): 112-114.
[15] Chakraborty J, Below AA, Solaiman D. Tamm-Horsfall protein in patients with kidney damage and diabetes[J]. Urol Res, 2004, 32(2): 79-83.
[16] 高欢. 脐带间充质干细胞对高糖环境下肾小管上皮细胞自噬的作用及相关机制研究[D].长春: 吉林大学, 2024.
[17] Immler R, Lange-Sperandio B, Steffen T, et al. Extratubular polymerized uromodulin induces leukocyte recruitment and inflammation in vivo[J]. Front Immunol, 2020, 11: 588245.