title: Maternal protein restriction reduces perlecan at mid-metanephrogenesis in rats.
abstract: OBJECTIVE
  Maternal dietary protein restriction reduces nephron number in offspring and increases the risk of cardiovascular and chronic kidney diseases. Perlecan is the major basement membrane/extracellular matrix heparan sulfate proteoglycan (HSPG) that plays a crucial role in nephron formation. This study was to determine whether maternal dietary protein restriction during pregnancy leads to an abnormal perlecan expression pattern during kidney development and a correlation with aberrant cell proliferation and apoptosis.
  
  
  METHODS
  Pregnant Sprague-Dawley rats were divided into two groups, maintained on either a low-protein diet (MLP group) or a normal-protein diet (MNP group). Kidneys were dissected from embryos of different kidney development stages. Real-time PCR and immunohistochemistry were performed to detect the transcript level of rHSPG2, the coding gene of perlecan, and its protein expression pattern. Apoptosis and proliferation cell were detected by TUNEL system and Ki67 marker.
  
  
  RESULTS
  Embryonic weights and nephron number were significantly affected by maternal low protein diets. The transcript level of rHSPG2 in the MLP group was significantly lower at embryonic day 18 and the neonatal period. Immunohistochemistry study was consistent with the RT-PCR results. The proliferation level of the MLP group was significantly lower than the MNP group at E18 and more apoptotic cells was detected in MLP newborn.
  
  
  CONCLUSIONS
  Maternal protein restriction reduced the expression of perlecan and lead aberrant cell proliferation and apoptosis during mid-metanephrogenesis in offspring. This data may provide new evidence to understand the mechanism of reduced nephron number due to maternal protein restriction and enlighten solution.
authors.affiliation: Department of Nephrology and Rheumatology, Children's Hospital of Fudan University, Shanghai, China.
authors.forename: Xiao-Shan
authors.initials: XS
authors.lastname: Tang
authors.affiliation: Department of Nephrology and Rheumatology, Children's Hospital of Fudan University, Shanghai, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Shen
authors.affiliation: Department of Nephrology and Rheumatology, Children's Hospital of Fudan University, Shanghai, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Chen
authors.affiliation: Department of Biochemistry and Molecular Biology, Shanghai Medical College, Fudan University, Shanghai, China.
authors.forename: Xi-Liang
authors.initials: XL
authors.lastname: Zha
authors.affiliation: Department of Nephrology and Rheumatology, Children's Hospital of Fudan University, Shanghai, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Xu
mesh_terms: D000824:Animal Nutritional Physiological Phenomena; D000818:Animals; D017209:Apoptosis; D049109:Cell Proliferation; D018753:Diet, Protein-Restricted; D015536:Down-Regulation; D005260:Female; D018507:Gene Expression Regulation, Developmental; D005865:Gestational Age; D019812:Heparan Sulfate Proteoglycans / Q000235:genetics / Q000378:metabolism*; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000378:metabolism; D039382:Maternal Nutritional Physiological Phenomena; D009399:Nephrons / Q000196:embryology / Q000378:metabolism*; D009752:Nutritional Status; D038081:Organogenesis; D011247:Pregnancy; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D019812:Heparan Sulfate Proteoglycans; D019394:Ki-67 Antigen; D012333:RNA, Messenger; C071927:perlecan
keywords: apoptosis; heparan sulphate; intrauterine growth; proliferation; renal development