- PhD: University of Edinburgh, Edinburgh, United Kingdom (2003)
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Claudins, salt resorption, fluid balance, hypomagnesemia, hypercalciuria, hypochloremia, hypertension, kidney stones.
Epithelia permit selective and regulated flux from apical to basolateral surfaces by transcellular passage through cells or paracellular flux between cells. Claudins are the key components of the paracellular pathway. Defects in claudin function result in a broad range of renal diseases, including hypomagnesemia, hypercalciuria, hypochloremia and salt-sensitive hypertension. Nevertheless, the roles of claudins in renal handling of electrolytes are largely elusive. Our lab develops transgenic siRNA mouse models to manipulate claudin expression in vivo and study their functions in paracellular transport of electrolytes. Our research interests are:
- Study paracellular reabsorption of magnesium in the Henle’s loop. The renal reabsorption of Mg2+ is primarily handled by the thick ascending limb (TAL) of Henle’s loop through the paracellular pathway. Its major constituents are claudin-16 and claudin-19. We have developed claudin-16 knockdown (KD) and claudin-19 KD mouse lines. Claudin-16 KD animals show chronic renal wasting of magnesium and calcium, developing nephrocalcinosis comparable to human FHHNC phenotypes. Future studies will show if the interaction between claudin-16 and claudin-19 is required for normal function of the TAL.
- Study distal paracellular reabsorption of chloride. The paracellular reabsorption of Cl- in the collecting duct is important for renal handling of salt and managing blood pressure. Claudin-4 and claudin-8 are key molecular components of this pathway. To elucidate their functions, we will generate claudin-4 KD and claudin-8 KD mice and analyze them for defects in chloride homeostasis.
- Study proximal paracellular salt reabsorption. The paracellular pathway in the proximal tubule is critical for salt reabsorption owing to its leaky tight junction and consists of claudin-2 and claudin-18. Using tissue-specific siRNA transgenic strategy, we will generate claudin-2 KD and claudin-18 KD in the proximal tubule of mouse kidney. These animals will be important tools to understand the paracellular transport function of the proximal tubule.
Gong Y, Wang J, Yang J, Gonzales E, Perez R, Hou J. KLHL3 regulates paracellular chloride transport in the kidney by ubiquitination of claudin-8. Proc Natl Acad Sci U S A. 2015 Apr 7;112(14):4340-5. doi:10.1073/pnas.1421441112. Epub 2015 Mar 23. PubMed PMID: 25831548; PubMed Central PMCID: PMC4394310.
Gong Y, Yu M, Yang J, Gonzales E, Perez R, Hou M, Tripathi P, Hering-Smith KS, Hamm LL, Hou J. The Cap1-claudin-4 regulatory pathway is important for renal chloride reabsorption and blood pressure regulation. Proc Natl Acad Sci U S A.
2014 Sep 9;111(36):E3766-74. doi: 10.1073/pnas.1406741111. Epub 2014 Aug 25. PubMed PMID: 25157135; PubMed Central PMCID: PMC4246945.
Gong Y, Himmerkus N, Plain A, Bleich M, Hou J. Epigenetic regulation of microRNAs controlling CLDN14 expression as a mechanism for renal calcium handling. J Am Soc Nephrol. 2015 Mar;26(3):663-76. doi: 10.1681/ASN.2014020129. Epub 2014 Jul 28. PubMed PMID: 25071082; PubMed Central PMCID: PMC4341477.
Gong Y, Hou J. Claudin-14 underlies Ca⁺⁺-sensing receptor-mediated Ca⁺⁺ metabolism via NFAT-microRNA-based mechanisms. J Am Soc Nephrol. 2014 Apr;25(4):745-60. doi: 10.1681/ASN.2013050553. Epub 2013 Dec 12. PubMed PMID: 24335970; PubMed Central PMCID: PMC3968499.
Gong Y, Renigunta V, Himmerkus N, Zhang J, Renigunta A, Bleich M, Hou J. Claudin-14 regulates renal Ca(++) transport in response to CaSR signalling via a novel microRNA pathway. EMBO J. 2012 Feb 28. doi: 10.1038/emboj.2012.49. [Epub ahead of print] PubMed PMID: 22373575.
Hou J, Renigunta A, Yang J, Waldegger S. Claudin-4 forms paracellular chloride channel in the kidney and requires claudin-8 for tight junction localization. Proc Natl Acad Sci U S A. 2010 Oct 19;107(42):18010-5. Epub 2010 Oct 4. PubMed PMID: 20921420; PubMed Central PMCID: PMC2964195.
Hou J, Renigunta A, Gomes AS, Hou M, Paul DL, Waldegger S, Goodenough DA. Claudin-16 and claudin-19 interaction is required for their assembly into tight junctions and for renal reabsorption of magnesium. Proc Natl Acad Sci U S A. 2009 Sep 8;106(36):15350-5. Epub 2009 Aug 24. PubMed PMID: 19706394; PubMed Central PMCID: PMC2741254.
Hou J, Renigunta A, Konrad M, Gomes AS, Schneeberger EE, Paul DL, Waldegger S, Goodenough DA. Claudin-16 and claudin-19 interact and form a cation-selective tight junction complex. J Clin Invest. 2008 Feb;118(2):619-28. PubMed PMID: 18188451; PubMed Central PMCID: PMC2176193.
Hou J, Shan Q, Wang T, Gomes AS, Yan Q, Paul DL, Bleich M, Goodenough DA. Transgenic RNAi depletion of claudin-16 and the renal handling of magnesium. J Biol Chem. 2007 Jun 8;282(23):17114-22. Epub 2007 Apr 18. PubMed PMID: 17442678.
Hou J, Gomes AS, Paul DL, Goodenough DA. Study of claudin function by RNA interference. J Biol Chem. 2006 Nov 24;281(47):36117-23. Epub 2006 Oct 3. PubMed PMID: 17018523.
Hou J, Paul DL, Goodenough DA. Paracellin-1 and the modulation of ion selectivity of tight junctions. J Cell Sci. 2005 Nov 1;118(Pt 21):5109-18. Epub 2005 Oct 18. PubMed PMID: 16234325.