Jianghui Hou, Ph.D.

Associate Professor
Internal Medicine
Renal

Molecular Cell Biology Program

  • 314-362-5685

  • 314-362-6419

  • 314-747-2435

  • 314-362-8237

  • 8126

  • Barnard Building #7748-7749

  • jhou@WUSTL.EDU

  • https://renal.wustl.edu/bio/jianghui-hou-phd/

  • biochemistry, biophysics, hypertension, ion channel, molecular medicine, transgenic

  • Cell-cell junctions that form epithelial barriers to ions and solutes critical for normal kidney functions

Research Abstract:

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:

(1) 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.

(2) 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.

(3) 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

Selected Publications:

1: Gong Y, Himmerkus N, Sunq A, Milatz S, Merkel C, Bleich M, Hou J. ILDR1 is
important for paracellular water transport and urine concentration mechanism.
Proc Natl Acad Sci U S A. 2017 May 1. pii: 201701006. doi:
10.1073/pnas.1701006114. [Epub ahead of print] PubMed PMID: 28461473.


2: Sato T, Courbebaisse M, Ide N, Fan Y, Hanai JI, Kaludjerovic J, Densmore MJ,
Yuan Q, Toka HR, Pollak MR, Hou J, Lanske B. Parathyroid hormone controls
paracellular Ca(2+) transport in the thick ascending limb by regulating the
tight-junction protein Claudin14. Proc Natl Acad Sci U S A. 2017 Apr
18;114(16):E3344-E3353. doi: 10.1073/pnas.1616733114. Epub 2017 Apr 3. PubMed
PMID: 28373577; PubMed Central PMCID: PMC5402431.


3: Milatz S, Himmerkus N, Wulfmeyer VC, Drewell H, Mutig K, Hou J, Breiderhoff T,
Müller D, Fromm M, Bleich M, Günzel D. Mosaic expression of claudins in thick
ascending limbs of Henle results in spatial separation of paracellular Na+ and
Mg2+ transport. Proc Natl Acad Sci U S A. 2017 Jan 10;114(2):E219-E227. doi:
10.1073/pnas.1611684114. Epub 2016 Dec 27. PubMed PMID: 28028216; PubMed Central
PMCID: PMC5240732.


4: Gong Y, Hou J. Claudins in barrier and transport function-the kidney. Pflugers
Arch. 2017 Jan;469(1):105-113. doi: 10.1007/s00424-016-1906-6. Epub 2016 Nov 23.
Review. PubMed PMID: 27878608; PubMed Central PMCID: PMC5203960.


5: Zhou L, Gong Y, Sunq A, Hou J, Baker LA. Capturing Rare Conductance in
Epithelia with Potentiometric-Scanning Ion Conductance Microscopy. Anal Chem.
2016 Oct 4;88(19):9630-9637. Epub 2016 Sep 23. PubMed PMID: 27618532.


6: Gong Y, Sunq A, Roth RA, Hou J. Inducible Expression of Claudin-1 in
Glomerular Podocytes Generates Aberrant Tight Junctions and Proteinuria through
Slit Diaphragm Destabilization. J Am Soc Nephrol. 2017 Jan;28(1):106-117. doi:
10.1681/ASN.2015121324. Epub 2016 May 5. PubMed PMID: 27151920; PubMed Central
PMCID: PMC5198280.


7: Gong Y, Renigunta V, Zhou Y, Sunq A, Wang J, Yang J, Renigunta A, Baker LA,
Hou J. Biochemical and biophysical analyses of tight junction permeability made
of claudin-16 and claudin-19 dimerization. Mol Biol Cell. 2015 Dec
1;26(24):4333-46. doi: 10.1091/mbc.E15-06-0422. Epub 2015 Oct 7. PubMed PMID:
26446843; PubMed Central PMCID: PMC4666130.


8: 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.


9: 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.


10: 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.

Last Updated: 5/5/2017 8:02:58 AM

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