Role of complement 3a in the growth of mesangial cells from stroke-prone spontaneously hypertensive rats.

Abstract

Vascular smooth muscle cells (VSMCs) derived from spontaneously hypertensive rats (SHR) show exaggerated growth with a synthetic phenotype and angiotensin II (Ang II) production associated with increased production of complement (C3). We hypothesized that C3 is involved in the growth of mesangial cells (MCs) from hypertensive rats. We examined the effects of a C3a receptor inhibitor on proliferation, phenotype and Ang II generation in MCs from stroke prone-spontaneously hypertensive rats (SHR)-SP, SHR and Wistar-Kyoto (WKY) rats. Expression of C3 and C3a receptor were evaluated by immunohistochemical staining of the renal cortex. We examined the effects of the C3a inhibitor, SB290157, on proliferation, the expression of phenotype-marker mRNAs and Ang II production in cells from SHR-SP, SHR and WKY rats. Immunostaining of C3 was stronger in SHR and SHRSP glomeruli. MCs from SHR-SP and SHR abundantly express pre-pro C3 mRNA. SB290157 significantly inhibited basal DNA synthesis and proliferation of MCs from SHR-SP and SHR. Expression of osteopontin mRNA in MCs from SHR-SP and SHR was decreased with SB290157 treatment, whereas MC basal expression of α-SMA mRNA was decreased. SB290157 significantly decreased the production of Ang II in MCs from SHR-SP and SHR. Endogenous C3a promotes exaggerated growth with a synthetic phenotype and the production of Ang II in MCs from SHR-SP and SHR. The C3 and C3a receptor system may primarily be involved in the pathogenesis of renal remodeling in hypertensive rats.

• Authors: Kazuya Ikeda, Noboru Fukuda, Takahiro Ueno, Morito Endo, Naohiko Kobayashi, Masayoshi Soma, Koichi Matsumoto
• Journal: Clinical and experimental hypertension (New York, N.Y. : 1993) (Clin Exp Hypertens) Vol. 36 Issue 1 Pg. 58-63 ( 2014) ISSN: 1525-6006 [Electronic] England
• PMID: 23713944 (Publication Type: Journal Article)

Chemical References

• Actins
• Benzhydryl Compounds
• RNA, Messenger
• Receptors, Complement
• SB 290157
• Spp1 protein, rat
• complement C3a receptor
• smooth muscle actin, rat
• Osteopontin
• Angiotensin II
• Complement C3a
• Arginine

Topics

• Actins (genetics)
• Angiotensin II (biosynthesis)
• Animals
• Arginine (analogs & derivatives, pharmacology)
• Benzhydryl Compounds (pharmacology)
• Cell Proliferation (drug effects)
• Complement C3a (genetics, metabolism)
• Gene Expression (drug effects)
• Hypertension (complications, metabolism, pathology)
• Kidney Cortex (metabolism, pathology)
• Male
• Mesangial Cells (drug effects, metabolism, pathology)
• Myocytes, Smooth Muscle (drug effects, metabolism, pathology)
• Osteopontin (genetics)
• RNA, Messenger (genetics, metabolism)
• Rats
• Rats, Inbred SHR
• Rats, Inbred WKY
• Receptors, Complement (antagonists & inhibitors, metabolism)
• Stroke (etiology, metabolism, pathology)