Upregulation of thymidine phosphorylase in chronic glomerulonephritis and its role in tubulointerstitial injury.
Chronic tubulointerstitial injury (CTI), commonly a sequel to chronic glomerulonephritis (CGN), is associated with the proliferation of new blood vessels. Angiogenesis is an essential process in chronic inflammation, and is controlled by a number of angiogenic factors including thymidine phosphorylase (TP). Knowledge of TP in renal disease is still rudimentary, and its role in CGN has not been explored. We analyzed the expression of TP by RTPCR, immunohistology and in situ hybridization in 20 human kidneys with CGN. To evaluate the degree of angiogenesis, we counted the microvessel density (MVD). MVD was significantly higher in all categories of CGN, between 19.7 +/- 7.7 and 58.9 +/- 7.5, compared to control value, 12.7 +/- 5.0 (p < 0.05). MVD was increased in areas of abundant mononuclear cell infiltration with minimal interstitial fibrosis, and decreased or absent in areas of marked fibrosis. There was a significant correlation between MVD and interstitial fibrosis (p < 0.0001). TP mRNA was upregulated for all categories of CGN. TP was strongly expressed by mononuclear inflammatory cells and in most atrophic tubules. Each MVD and interstitial volume was significantly correlated with both the number of TP+ mononuclear cells and TP+ tubular cells, respectively (p < 0.0001). We have demonstrated an upregulation of TP and increase in MVD in areas of CTI in a variety of CGN. The up-regulation of TP may contribute to angiogenesis, which may play a critical role in the progression of interstitial fibrosis in CGN.
Wang
Eun-Hui
EH
Department of Clinical Pathology, Surgery, Pharmacology and Urology, The Catholic University of Korea, Seoul, Korea.
Goh
Yong Bok
YB
Moon
In Sung
IS
Park
Cho Hyun
CH
Lee
Kweon-Heang
KH
Kang
Sung Hak
SH
Kang
Chang Suk
CS
Choi
Yeong-Jin
YJ
D000328:Adult; D002908:Chronic Disease; D018450:Disease Progression; D005260:Female; D005921:Glomerulonephritis / Q000150:complications* / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009389:Neovascularization, Pathologic; D013939:Thymidine Phosphorylase / Q000096:biosynthesis*; D015854:Up-Regulation
D013939:Thymidine Phosphorylase