Albuminuria is the hallmark of nephrotic syndrome (NS), a leading cause of chronic kidney disease that affects 500 million people worldwide, but the molecular mechanism underlying albuminuria-induced kidney injury remains poorly defined.
Using a genetic model of nephrotic syndrome and an acquired model of focal segmental glomerulosclerosis, Sun-Ji Park, PhD, in her second first-author PNAS paper resulting from her post-doctoral studies, identified CHOP (C/EBP homologous protein)-TXNIP (thioredoxin-interacting protein) as critical molecular linkers between albuminuria-induced ER dysfunction and mitochondria dyshomeostasis.
We showed that TXNIP relocates from the nucleus to mitochondria when CHOP is induced by albuminuria. Blocking CHOP-dependent TXNIP shuttling to the mitochondria attenuates albuminura and mitigates kidney injury in NS. We have also collaborated with Dr. Sharma to utilize his newly invented PET/CT molecular imaging probe to detect kidney ROS in live animals for the first time.
Dr. Sun-Ji Park is currently working at the New Drug Development Center, South Korea. Read about her first PNAS article (2019) here. Yeawon Kim, the Lab Supervisor and Dr. Chuang Li, a Postdoc in the lab, also made significant contributions to the project.
Read the current article, published August 22, 2022, in PNAS here: Authors: Sun-Ji Park , Yeawon Kim , Chuang Li , Junwoo Suh , Jothilingam Sivapackiam , Tassia M Goncalves , George Jarad , Guoyan Zhao, Fumihiko Urano, Vijay Sharma, Ying Maggie Chen.
The article was highlighted in the August 31, 2022, ASN in the Loop daily news briefing.