[The role of AT1 receptor and cyclin kinase inhibitor p27 protein in angiotensin II-induced hypertrophy of mesangial cell].
OBJECTIVE
To investigate the role of p27 and AT1 receptor in the hypertrophy of mesangial cell (MC) induced by angiotensin II (Ang II).


METHODS
p27 protein of MC lysate was detected with Western blotting analysis. The degree of cultured MC hypertrophy was estimated through [3H] thymidine incorporation and [3H] leucine incorporation. The effect of reducing p27 expression on cell hypertrophy was analysed with p27 antisense oligodeoxynucleotide (ODN) phosphorothioate. The extracellular matrix (ECM) protein (type IV collagen and fibronectin) of MC lysate was examined with ELISA.


RESULTS
Ang II stimulated p27 expression of MC cultured in normal glucose DMEM. MC stimulated by Ang II revealed hypertrophy as well as increased [3H] leucine incorporation, decreased [3H] thymidine incorporation and increased ECM. p27 antisense ODN transfection abolished the effect of Ang II mentioned above. Losartan lowered p27 level of MC stimulated by Ang II and attenuated MC hypertrophy induced by Ang II; meanwhile [3H] leucine incorporation and ECM level decreased, [3H] thymidine incorporation increased. The effect of Losartan was dose-dependent.


CONCLUSIONS
Ang II induced MC hypertrophy by increasing p27 protein level through AT1 receptor. Because the cell cycle is controlled by the interplay between the positive and negative cell cycle regulatory proteins (CCRP), further research is needed to study the expression of the positive and negative CCRP in MC in order to understand better the role of CCRP in MC hypertrophy induced by Ang II.
Mei
X
X
Department of Nephrology, Changhai Hospital, Second Military Medical University, Shanghai 200433, China.
Gao
C
C
Cui
R
R
D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D018797:Cell Cycle Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D002478:Cells, Cultured; D050760:Cyclin-Dependent Kinase Inhibitor p27; D005920:Glomerular Mesangium / Q000187:drug effects / Q000473:pathology*; D006984:Hypertrophy / Q000139:chemically induced / Q000473:pathology; D019808:Losartan / Q000494:pharmacology; D020319:Oligodeoxyribonucleotides, Antisense / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D044140:Receptor, Angiotensin, Type 1; D011945:Receptors, Angiotensin / Q000502:physiology*; D025521:Tumor Suppressor Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*
D000959:Antihypertensive Agents; C493962:Cdkn1b protein, rat; D018797:Cell Cycle Proteins; D020319:Oligodeoxyribonucleotides, Antisense; D044140:Receptor, Angiotensin, Type 1; D011945:Receptors, Angiotensin; D025521:Tumor Suppressor Proteins; D000804:Angiotensin II; D050760:Cyclin-Dependent Kinase Inhibitor p27; D019808:Losartan