N-Acetyl-seryl-aspartyl-lysyl-proline Alleviates Renal Fibrosis Induced by Unilateral Ureteric Obstruction in BALB/C Mice.
To expand the armamentarium of treatment for chronic kidney disease (CKD), we explored the utility of boosting endogenously synthesized N-acetyl-seryl-aspartyl-lysyl-proline (Ac-SDKP), which is augmented by inhibition of the angiotensin converting enzyme. Male BALB/c mice underwent unilateral ureteral ligation (UUO) or sham operation and received exogenously administered Ac-SDKP delivered via a subcutaneous osmotic minipump or Captopril treatment by oral gavage. Seven days after UUO, there were significant reductions in the expression of both collagen 1 and collagen 3 in kidneys treated with Ac-SDKP or Captopril, and there was a trend towards reductions in collagen IV, α-SMA, and MCP-1 versus control. However, no significant attenuation of interstitial injury or macrophage infiltration was observed. These findings are in contrary to observations in other models and underscore the fact that a longer treatment time frame may be required to yield anti-inflammatory effects in BALB/c mice treated with Ac-SDKP compared to untreated mice. Finding an effective treatment regimen for CKD requires fine-tuning of pharmacologic protocols.
Division of Nephrology, Department of Medicine, The University of Hong Kong, Hong Kong.
Gary C W
GC
Chan
Division of Nephrology, Department of Medicine, The University of Hong Kong, Hong Kong.
Wai Han
WH
Yiu
Division of Nephrology, Department of Medicine, The University of Hong Kong, Hong Kong.
Hao Jia
HJ
Wu
Division of Nephrology, Department of Medicine, The University of Hong Kong, Hong Kong.
Dickson W L
DW
Wong
Division of Nephrology, Department of Medicine, The University of Hong Kong, Hong Kong.
Miao
M
Lin
Department of Medicine and Therapeutics and Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong.
Xiao Ru
XR
Huang
Department of Medicine and Therapeutics and Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong.
Hui Yao
HY
Lan
Division of Nephrology, Department of Medicine, The University of Hong Kong, Hong Kong.
Sydney C W
SC
Tang
D000199:Actins / Q000378:metabolism; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use; D000818:Animals; D002216:Captopril / Q000737:chemistry; D018932:Chemokine CCL2 / Q000378:metabolism; D024141:Collagen Type IV / Q000378:metabolism; D005355:Fibrosis / Q000188:drug therapy*; D007150:Immunohistochemistry; D007249:Inflammation; D007674:Kidney Diseases / Q000188:drug therapy*; D008214:Lymphocytes / Q000166:cytology; D008264:Macrophages / Q000166:cytology / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009130:Muscle, Smooth / Q000378:metabolism; D009842:Oligopeptides / Q000627:therapeutic use*; D060888:Real-Time Polymerase Chain Reaction; D014517:Ureteral Obstruction / Q000188:drug therapy*
D000199:Actins; D000806:Angiotensin-Converting Enzyme Inhibitors; C111835:CCL2 protein, human; D018932:Chemokine CCL2; D024141:Collagen Type IV; D009842:Oligopeptides; D002216:Captopril; C058504:goralatide