Enhanced Autophagy in Polycystic Kidneys of AQP11 Null Mice

Yasuko Tanaka; Mayumi Watari; Tatsuya Saito; Yoshiyuki Morishita; Kenichi Ishibashi
December 2016
International Journal of Molecular Sciences;Dec2016, Vol. 17 Issue 12, p1993
Academic Journal
Aquaporin-11 (AQP11) is an intracellular water channel expressed at the endoplasmic reticulum (ER) of the proximal tubule. Its gene disruption in mice leads to intracellular vacuole formation at one week and the subsequent development of polycystic kidneys by three weeks. As the damaged proximal tubular cells with intracellular vacuoles form cysts later, we postulated that autophagy may play a role in the cyst formation and examined autophagy activity before and after cyst development in AQP11(-/-) kidneys. PCR analysis showed the increased expression of the transcript encoding LC3 (Map1lc3b) as well as other autophagy-related genes in AQP11(-/-) mice. Using green fluorescent protein (GFP)-LC3 transgenic mice and AQP11(-/-) mice, we found that the number of GFP-LC3-positive puncta was increased in the proximal tubule of AQP11(-/-) mice before the cyst formation. Interestingly, they were also observed in the cyst-lining epithelial cell. Further PCR analyses revealed the enhanced expression of apoptosis-related and ER stress-related caspase genes before and after the cyst formation, which may cause the enhanced autophagy. These results suggest the involvement of autophagy in the development and maintenance of kidney cysts in AQP11(-/-) mice.


Related Articles

  • Autophagy: Pinpointing the mysterious membrane donors. David, Rachel // Nature Reviews Molecular Cell Biology;Apr2013, Vol. 14 Issue 4, p194 

    The article focuses on a study conducted by researchers which reveals that autophagosomes orininate at contact sites of endoplasmic reticulum (ER)-mitochondria in mammalian cells.

  • HDLs inhibit endoplasmic reticulum stress and autophagic response induced by oxidized LDLs. Muller, C.; Salvayre, R.; Nègre-Salvayre, A.; Vindis, C. // Cell Death & Differentiation;May2011, Vol. 18 Issue 5, p817 

    The apoptotic effect of oxidized LDLs (oxLDLs) is mediated through a complex sequence of signaling events involving a deregulation of the cytosolic Ca2+ homeostasis. OxLDLs also trigger ER stress that may lead to cellular dysfunction and apoptosis, through the activation of the IRE1α/c-Jun...

  • Curvature of Double-Membrane Organelles Generated by Changes in Membrane Size and Composition. Knorr, Roland L.; Dimova, Rumiana; Lipowsky, Reinhard // PLoS ONE;Mar2012, Vol. 7 Issue 3, p1 

    Transient double-membrane organelles are key players in cellular processes such as autophagy, reproduction, and viral infection. These organelles are formed by the bending and closure of flat, double-membrane sheets. Proteins are believed to be important in these morphological transitions but...

  • Compartmentalized regulation of autophagy regulators: fine-tuning AMBRA1 by Bcl-2. Tooze, Sharon A; Codogno, Patrice // EMBO Journal;4/6/2011, Vol. 30 Issue 7, p1185 

    No abstract available.

  • Na+/H+ exchanger-1 reduces podocyte injury caused by endoplasmic reticulum stress via autophagy activation. Feng, Zhe; Tang, Li; Wu, Lingling; Cui, Shaoyuan; Hong, Quan; Cai, Guangyan; Wu, Di; Fu, Bo; Wei, Ribao; Chen, Xiangmei // Laboratory Investigation (00236837);Apr2014, Vol. 94 Issue 4, p439 

    Podocyte injury has a critical role in the pathogenesis of proteinuria. Induction of endoplasmic reticulum (ER) stress is thought to lead to podocyte injury; however, no effective strategy for reducing ER stress-induced injury has been identified. We investigated specific mechanisms for reducing...

  • The origin of the autophagosomal membrane. Tooze, Sharon A.; Yoshimori, Tamotsu // Nature Cell Biology;Sep2010, Vol. 12 Issue 9, p831 

    Macroautophagy is initiated by the formation of the phagophore (also called the isolation membrane). This membrane can both selectively and non-selectively engulf cytosolic components, grow and close around the sequestered components and then deliver them to a degradative organelle, the...

  • The Enigmatic MEMBRANE. Man, Muriel; Tooze, Sharon A.; Reggioni, Fulvio // Scientist;Feb2012, Vol. 26 Issue 2, p34 

    The article focuses on the formation, distinction, and origin of autophagosomes. It states that endoplasmic reticulum (ER), which is responsible for the production of lipids and proteins, is the first organelle to be considered as the source of autophagosomal membranes. It also discusses steps...

  • Endoplasmic reticulum stress induces autophagy in renal proximal tubular cells. Kawakami, Takahisa; Inagi, Reiko; Takano, Hideki; Sato, Shigeru; Ingelfinger, Julie R.; Fujita, Toshiro; Nangaku, Masaomi // Nephrology Dialysis Transplantation;Sep2009, Vol. 24 Issue 9, p2665 

    Background. Autophagy, an intracellular self-degradation system conserved throughout eukaryotes, plays an important role in a variety of biological processes, including cell death, development, cancer, defence against infection and neurodegeneration. However, little information about autophagy...

  • Expression of Derlin-1 and its effect on expression of autophagy marker genes under endoplasmic reticulum stress in lung cancer cells. Li Xu; Zan-Hong Wang; Dong Xu; Gang Lin; Dai-Rong Li; Tao Wan; Shu-Liang Guo // Cancer Cell International;2014, Vol. 14 Issue 1, p1 

    Background Recent findings indicated that Derlin-1 has an important function in tumour progression. In this study, we aimed to determine whether Derlin-1 has an oncogene function as a cross-talk molecule with autophagy. Methods Cancer cells were treated with tunicamycin (TM) for 8 and 24 h. The...

  • Dengue Virus and Autophagy. Heaton, Nicholas S.; Randall, Glenn // Viruses (1999-4915);Aug2011, Vol. 3 Issue 8, p1332 

    Several independent groups have published that autophagy is required for optimal RNA replication of dengue virus (DENV). Initially, it was postulated that autophagosomes might play a structural role in replication complex formation. However, cryo-EM tomography of DENV replication complexes...


Read the Article


Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics