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Daohong Lin, Ph.D.

Daohong Lin, Ph.D.Assistant Professor

E-mail: daohong_lin@nymc.edu

Tel: (914) 594-3870/4120


Department of Pharmacology
Basic Science Building, Rm. 534
15 Dana Road
Valhalla, NY  10595

Professional Interests:

Inwardly rectifying potassium channels (Kirs) play a critical role in mediating renal K secretion. We have found that basolateral Kcnj10 expression determines the apical Na-Cl cotransporter in distal convoluted tubule (DCT). However, the underlying mechanism remains largely unknown. My research goal is to explore the mechanism of posttranslational regulation of Kirs channels in the non-excitable epithelial cells, such as renal DCT cells, in response to low potassium diet intake. In addition, I have demonstrated that Kcnj10 is a major Kir channel and determines the membrane potential in corneal epithelial cell. Furthermore, my recent work shows that miR-205 plays an important role in promoting the healing process of corneal epithelium and that the beneficial effect of microRNA is achieved by the inhibition of Kir.4.1. My current ongoing research interest expands to study the effects of Kirs regulation in modulating cell migration during corneal wound healing.

KCNJ10 (Kir4.1) is expressed in the basolateral membrane of the cortical thick ascending limb.

Inwardly rectifier K channels (Kirs) encoded by the KCNJ genes are responsible for generating the cell membrane potential. Kir is constitutively active in cell membranes, favoring K influx more than efflux crossing membrane, thereby modulating membrane potential, K+ hemostasis and trans-epithelial voltage gradient. Loss-of-function mutations in KCNJ10 have been associated with the autosomal recessive SeSAME syndrome (Seizures, Sensorineural deafness, Ataxia, Mental retardation, and Electrolyte imbalance, SeSAME), also known as EAST syndrome (Epilepsy, Ataxia, Sensorineural deafness, and Tubulopathy, EAST). By using Kcnj10+/+ wild-type (WT) and Kcnj10-/- knockout (KO) mice, we have found that Kcnj10 (Kir4.1) in contributing to the basolateral K conductance in the cortical thick ascending limb (cTAL). Moreover, the gene disruption of Kcnj10 did not affect the expression of Na-K-Cl cotransporter 2 (NKCC2) but determines the apical Na-Cl cotransporter (NCC) expression in DCT, possibly through a Ste20-related proline-alanine-rich kinase-dependent mechanism (Fig.1).

The role and regulation of Kir4.1 in healing process after injury in corneal epithelial cells (CECs).

The aim of the study is to test the hypotheses that injury stimulates the expression of miR-205, which in turn inhibits KCNJ10 channels by targeting its 3'-UTR, thereby facilitating the wound healing process in CECs. The scratch injury in CECs increased the expression of miR-205 and decreased the expression of Kcnj10 within 24 h. The notion that miR-205 may target Kcnj10 was supported by dual luciferase reporter assay showing an inhibitive effect of miR-205 on 3' UTR of Kcnj10. Application of miR-205 antagomer significantly delayed the regrowth in wounded CECs. However, inhibition of Kcnj10 partially abolished the effect from miR-205 antagomer and restored the healing process. Moreover, over-expression miR-205 antagomer enhanced the protein expression of Kcnj10 but not Kcnj16. In addition, patch-clamp demonstrated that inhibition of endogenous miR-205 expression increased Ba2+-sensitive inwardly rectifying K+ channels. In addition, an electrophysiological study of CECs showed the presence of Kcnj10-like 20 pS K+ channels and scratch- injury significantly decreased the Ba2+-sensitive inwardly-rectifying K+ currents. We conclude that miR-205 stimulates wound healing by inhibiting its target gene Kcnj10.

Selected Publications:

  1. Lin, DH; Yue P.; Pan CY; and Sun P; Wang WH. MicroRNA 802 (miR-802) stimulates ROMK channels by suppressing caveolin-1 expression. JASN 22(6):1087-98, 2011.
  2. Peng Sun, Joseph Antoun, Dao-Hong Lin, Peng Yue, Katherine H. Gotlinger, Jorge Capdevila, Wen-Hui Wang. Cyp2c44 Epoxygenase Is Essential for Preventing the Renal Sodium Absorption During Increasing Dietary Potassium Intake.  Hypertension. 59(2):339-47, 2012.
  3. Dao-Hong Lin, Peng Yue, Jesse Rinehart, Peng Sun, Zhijian Wang, Richard Lifton, and Wen-Hui Wang. Protein phosphatase 1 modulates the inhibitory effect of With-no-Lysine kinase 4 on ROMK channels. Am J Physiol Renal Physiol 303:F110–F119, 2012.
  4. Peng Sun, Joseph Antoun, Dao-Hong Lin, Peng Yue, Katherine H. Gotlinger, Jorge Capdevila, Wen-Hui Wang, Cyp2c44-epoxygenase is essential for preventing the renal sodium absorption during increasing dietary potassium (K)-intake. Hypertension, 59:339-347, 2012. PMID: 22184322
  5. Yue P, Zhang C, Lin DH, Sun P, Wang WH. WNK4 inhibits Ca2+-activated big-conductance potassium channels (BK) via mitogen-activated protein kinase-dependent pathway. Biochim Biophys Acta 833(10):2101-10, 2013.
  6. Wang Z, Yue P, Lin DH, Wang WH. Carbon monoxide stimulates Ca2+ -dependent big-conductance K channels in the cortical collecting duct. Am J Physiol Renal Physiol. 304(5):F543-52, 2013
  7. Daohong Lin, Adna Halilovic, Peng Yue, Lars Bellner, Kemeng Wang, Sherin Thomas. Inhibition of miR-205 impairs the wound healing process in human corneal epithelial cells (HCEs) by targeting KIR4.1 KCNJ10). IOVS, 2013 Sep 11;54(9):6167-78.
  8. Zhang C, Wang L, Thomas S, Wang K, Lin DH, Rinehart J, Wang WH. Src family protein tyrosine kinase regulates the basolateral K channel in the distal convoluted tubule (DCT) by phosphorylation of KCNJ10 protein. J Biol Chem. 288(36):26135-46, 2013.
  9. Lin DH, Yue P, Zhang C, Wang WH. MicroRNA-194 (miR-194) regulates ROMK channel activity by targeting intersectin 1. Am J Physiol Renal Physiol 306(1):F53-60, 2014.
  10. Zhang C, Wang L, Zhang J, Su XT, Lin DH, Scholl UI, Giebisch G, Lifton RP, Wang WH. KCNJ10 determines the expression of the apical Na-Cl cotransporter (NCC) in the early distal convoluted tubule (DCT1). Proc Natl Acad Sci U S A. 2014 Aug 12;111(32):11864-9.
  11. Wang L, Zhang C, Su X, Lin D. Kcnj10 is a major type of K+ channel in mouse corneal epithelial cells and plays a role in initiating EGFR signaling. Am J Physiol Cell Physiol. 2014 Oct 15;307(8):C710-7.
  12. Zhang C, Wang L, Su XT, Lin DH, Wang WH. KCNJ10 (Kir4.1) is expressed in the basolateral membrane of the cortical thick ascending limb. Am J Physiol Renal Physiol. 2015 Jun 1;308(11):F1288-96.
  13. Wang L, Zhang C, Su X, Lin DH, Wang W. Caveolin-1 Deficiency Inhibits the Basolateral K+ Channels in the Distal Convoluted Tubule and Impairs Renal K+ and Mg2+ Transport. J Am Soc Nephrol. 2015 Nov;26(11):2678-90.
  14. Lin DH, Yue P, Yarborough O, Scholl UI, Giebisch G, Lifton RP, Rinehart J, Wang WH. Src-family protein tyrosine kinase phosphorylates WNK4 and modulates its inhibitory effect on KCNJ1 (ROMK). PNAS. 2015 Apr 7;112(14):4495-5000.

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