| First Author | Qin S | Year | 2012 |
| Journal | J Am Soc Nephrol | Volume | 23 |
| Issue | 8 | Pages | 1309-18 |
| PubMed ID | 22677559 | Mgi Jnum | J:316665 |
| Mgi Id | MGI:6840020 | Doi | 10.1681/ASN.2011030277 |
| Citation | Qin S, et al. (2012) c-Met and NF-kappaB-dependent overexpression of Wnt7a and -7b and Pax2 promotes cystogenesis in polycystic kidney disease. J Am Soc Nephrol 23(8):1309-18 |
| abstractText | The mechanisms of cystogenesis in autosomal dominant polycystic kidney disease (ADPKD) are not fully understood. Hyperactivation of the tyrosine kinase c-Met contributes to cyst formation, but we do not know the downstream mediators. Here, we found that hyperactivated c-Met led to increased NF-kappaB signaling, which in turn, drove de novo expression of Wnt7a and overexpression of Wnt7b in Pkd1(-/-) mouse kidneys. Hyperactivated Wnt signaling increased expression of the transcription factor Pax2 in the cells lining cysts. Furthermore, blocking Wnt signaling with DKK1 decreased cyst formation in an organ culture model of ADPKD. In summary, these results suggest that the c-Met/NF-kappaB/Wnt/Pax2 signaling transduction axis may provide pharmacological targets for the treatment of ADPKD. |
