HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE ADVANCED SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Fan, Q. Articles by Guan, N. PubMed Articles by Fan, Q. Articles by Guan, N.

¹ Department of Pediatrics, Peking University First Hospital, Beijing 100034, China
² Department of Pediatrics, Peking University Third Hospital, Beijing 100083, China
³ Department of Pediatrics, Fuzhou General Hospital, Fuzhou 350025, China

A lot of mutations of podocin, a key protein of podocyte slit diaphragm (SD), have been found both in hereditary and sporadic focal segmental glomeruloscleorosis (FSGS). Nevertheless, the mechanisms of podocyte injury induced by mutant podocins are still unclear. A compound heterozygous podocin mutation was identified in our FSGS patient, leading to a truncated (podocin ^V165X) and a missense mutant protein (podocin ^R168H), respectively. Here, it was explored whether and how both mutant podocins induce podocyte injury in the in vitro cultured podocyte cell line. Our results showed that podocin ^R168H induced more significant podocyte apoptosis and expression changes in more podocyte molecules than podocin ^V165X. Podocyte injury caused by the normal localized podocin^V165X was effectively inhibited by TRPC6 knockdown. The abnormal retention of podocin^R168H in endoplasmic reticulum (ER) resulted in the mis-localizations of other critical SD molecules nephrin, CD2AP and TRPC6, and significantly up-regulated ER stress markers Bip/grp78, p-PERK and caspase-12. These results implicated that podocin ^R168H and podocin ^V165X induced different degrees of podocyte injury, which might be resulted from different molecular mechanisms. Our findings provided some possible clues for further exploring the pharmacological targets to the proteinuria induced by different mutant podocins.

^* djnc_5855{at}126.com