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Balakuntalam S. Kasinath,
Professor, M.D.
Telephone: (210) 567-4707 E-mail: kasinath@uthscsa.edu The current focus of our investigations is on the role of protein translation in increasing the synthesis of extracellular matrix proteins in diabetic kidney disease. We employ both animal and renal cell culture models. We are exploring the regulation of eukaryotic initiation factors, e.g., eIF4E and its binding protein 4E-BP1, in promoting the synthesis of laminin in db/db mice with type 2 diabetes. As early stage of type 2 diabetes is associated with increased insulin levels, and as insulin is a powerful regulator of protein translation and eIF4E system, we are testing whether insulin augments protein translation of laminin by recruiting eIF4E pathway in the diabetic kidney. We are dissecting out the signaling pathways that may regulate eIF4E system both in the renal tissue of mice with type II diabetes and renal cells exposed to insulin. Our other area of interest is the potential role of vascular endothelial growth factor in diabetic kidney disease. VEGF is a major injurious factor in the development of diabetic eye disease. We have observed that VEGF expression is increased in the kidney in early stages of diabetes, suggesting it may contribute to growth and extracellular matrix changes in the diabetic kidney. We are exploring the cellular processes that are under VEGF regulation such as protein synthesis and synthesis of extracellular matrix proteins. We are investigating the signaling pathways recruited by VEGF receptors in altering cell functions. |
Schelling
JR, Abboud HE, Nicholas SB, Pahl MV, Sedor JR, Adler SG, Arar NH, Bowden
DW, Elston RC, Freedman BI, Goddard KA, Guo X, Hanson RL, Ipp E, Iyengar
SK, Jun G, Kao WH, Kasinath BS, Kimmel PL, Klag MJ, Knowler WC, Nelson
RG, Parekh RS, Quade SR, Rich SS, Saad MF, Scavini M, Smith MW, Taylor
K, Winkler CA, Zager PG, Shah VO; the Family Investigation of Nephropathy
and Diabetes Research Group.
Genome-Wide Scan for Estimated GFR in Multi-Ethnic Diabetic Populations:
The Family Investigation of Nephropathy and Diabetes.
Diabetes. 2007 Nov 14; [Epub ahead of print]
PMID: 18003762
Das
F, Mahimainathan L, Ghosh-Choudhury N, Venkatesan B, Kasinath BS, Abboud
HE, Ghosh Choudhury G.
TGFbeta intercepts nuclear glycogen synthase kinase 3beta to inhibit
PDGF-induced DNA synthesis in mesangial cells.
FEBS Lett. 2007 Nov 13;581(27):5259-67. Epub 2007 Oct 16.
PMID: 17961557
Sataranatarajan
K, Mariappan MM, Lee MJ, Feliers D, Choudhury GG, Barnes JL, Kasinath BS.
Regulation of Elongation Phase of mRNA Translation in Diabetic Nephropathy.
Amelioration by Rapamycin.
Am J Pathol. 2007 Nov 8; [Epub ahead of print]
PMID: 17991718
Feliers
D, Lee MJ, Ghosh-Choudhury G, Bomsztyk K, Kasinath BS.
Heterogeneous nuclear ribonucleoprotein K contributes to angiotensin
II stimulation of vascular endothelial growth factor mRNA translation.
Am J Physiol Renal Physiol. 2007 Aug;293(2):F607-15. Epub 2007
Jun 20.
PMID: 17581920
Lee
MJ, Feliers D, Mariappan MM, Sataranatarajan K, Mahimainathan L, Musi N,
Foretz M, Viollet B, Weinberg JM, Choudhury GG, Kasinath BS.
A role for AMP-activated protein kinase in diabetes-induced renal hypertrophy.
Am J Physiol Renal Physiol. 2007 Feb;292(2):F617-27. Epub 2006
Oct 3.
PMID: 17018841
Mariappan
MM, Feliers D, Mummidi S, Choudhury GG, Kasinath BS.
High glucose, high insulin, and their combination rapidly induce laminin-beta1
synthesis by regulation of mRNA translation in renal epithelial cells.
Diabetes. 2007 Feb;56(2):476-85.
PMID: 17259394
Kasinath
BS, Mariappan MM, Sataranatarajan K, Lee MJ, Feliers D.
mRNA translation: unexplored territory in renal science.
J Am Soc Nephrol. 2006 Dec;17(12):3281-92. Epub 2006 Sep 7.
Review.
PMID: 16959824
Feliers
D, Gorin Y, Ghosh-Choudhury G, Abboud HE, Kasinath BS.
Angiotensin II stimulation of VEGF mRNA translation requires production
of reactive oxygen species.
Am J Physiol Renal Physiol. 2006 Apr;290(4):F927-36. Epub 2005
Oct 25.
PMID: 16249273
Feliers
D, Chen X, Akis N, Choudhury GG, Madaio M, Kasinath BS.
VEGF regulation of endothelial nitric oxide synthase in glomerular
endothelial cells.
Kidney Int. 2005 Oct;68(4):1648-59.
PMID: 16164642
Mariappan
MM, Senthil D, Natarajan KS, Choudhury GG, Kasinath BS.
Phospholipase Cgamma-Erk Axis in vascular endothelial growth factor-induced
eukaryotic initiation factor 4E phosphorylation and protein synthesis in
renal epithelial cells.
J Biol Chem. 2005 Aug 5;280(31):28402-11. Epub 2005 May 26.
PMID: 15919658
Feliers
D, Duraisamy S, Barnes JL, Ghosh-Choudhury G, Kasinath BS.
Translational regulation of vascular endothelial growth factor expression
in renal epithelial cells by angiotensin II.
Am J Physiol Renal Physiol. 2005 Mar;288(3):F521-9. Epub 2004
Nov 30.
PMID: 15572520
Ha
TS, Duraisamy S, Faulkner JL, Kasinath BS.
Regulation of glomerular endothelial cell proteoglycans by glucose.
J Korean Med Sci. 2004 Apr;19(2):245-52.
PMID: 15082898
Kasinath
BS.
Lipoxygenases in renal injury--loading the matrix.
Kidney Int. 2003 Nov;64(5):1918-9. Review. No abstract available.
PMID: 14531829
Senthil
D, Choudhury GG, McLaurin C, Kasinath BS.
Vascular endothelial growth factor induces protein synthesis in renal
epithelial cells: a potential role in diabetic nephropathy.
Kidney Int. 2003 Aug;64(2):468-79.
PMID: 12846742
Senthil
D, Choudhury GG, Abboud HE, Sonenberg N, Kasinath BS.
Regulation of protein synthesis by IGF-I in proximal tubular epithelial
cells.
Am J Physiol Renal Physiol. 2002 Dec;283(6):F1226-36. Epub 2002
Aug 13.
PMID: 12388420
Rincon-Choles
H, Kasinath BS, Gorin Y, Abboud HE.
Angiotensin II and growth factors in the pathogenesis of diabetic nephropathy.
Kidney Int Suppl. 2002 Dec;(82):8-11.
PMID: 12410848
Senthil
D, Ghosh Choudhury G, Bhandari BK, Kasinath BS.
The type 2 vascular endothelial growth factor receptor recruits insulin
receptor substrate-1 in its signalling pathway.
Biochem J. 2002 Nov 15;368(Pt 1):49-56.
PMID: 12153400
Arar
NH, Plaetke R, Arar MY, Kasinath BS, Abboud HE.
Incorporating the Contextual Assessment Approach to regimens used in
genetic family studies.
Genet Med. 2002 Nov-Dec;4(6):451-63.
PMID: 12509718
Ding
G, Reddy K, Kapasi AA, Franki N, Gibbons N, Kasinath BS, Singhal PC.
Angiotensin II induces apoptosis in rat glomerular epithelial cells.
Am J Physiol Renal Physiol. 2002 Jul;283(1):F173-80.
PMID: 12060599
Singhal
PC, Bhaskaran M, Patel J, Patel K, Kasinath BS, Duraisamy S, Franki N,
Reddy K, Kapasi AA.
Role of p38 mitogen-activated protein kinase phosphorylation and Fas-Fas
ligand interaction in morphine-induced macrophage apoptosis.
J Immunol. 2002 Apr 15;168(8):4025-33.
PMID: 11937560
Senthil
D, Faulkner JL, Choudhury GG, Abboud HE, Kasinath BS.
Angiotensin II inhibits insulin-stimulated phosphorylation of eukaryotic
initiation factor 4E-binding protein-1 in proximal tubular epithelial cells.
Biochem J. 2001 Nov 15;360(Pt 1):87-95.
PMID: 11695995
Feliers
D, Duraisamy S, Faulkner JL, Duch J, Lee AV, Abboud HE, Choudhury GG, Kasinath
BS.
Activation of renal signaling pathways in db/db mice with type 2 diabetes.
Kidney Int. 2001 Aug;60(2):495-504.
PMID: 11473632
Bhandari
BK, Feliers D, Duraisamy S, Stewart JL, Gingras AC, Abboud HE, Choudhury
GG, Sonenberg N, Kasinath BS.
Insulin regulation of protein translation repressor 4E-BP1, an eIF4E-binding
protein, in renal epithelial cells.
Kidney Int. 2001 Mar;59(3):866-75.
PMID: 11231341
Sagireddy
PB, Pergola PE, Riley DJ, Boldt DH, Kasinath BS.
Non-clonal large granular cell lymphocytosis after renal transplantation.
Nephrol Dial Transplant. 2000 Sep;15(9):1485-6. No abstract
available.
PMID: 10978423
Ha
TS, Barnes JL, Stewart JL, Ko CW, Miner JH, Abrahamson DR, Sanes JR, Kasinath
BS.
Regulation of renal laminin in mice with type II diabetes.
J Am Soc Nephrol. 1999 Sep;10(9):1931-9.
PMID: 10477145
Johnson
LZ, Martinez I, Fernández MC, Davis CP, Kasinath BS.
Successful treatment of valproic acid overdose with hemodialysis.
Am J Kidney Dis. 1999 Apr;33(4):786-9.
PMID: 10196025
Bradley
J, Forero N, Pho H, Escobar B, Kasinath BS, Anzueto A.
Progressive somnolence leading to coma in a 68-year-old man.
Chest. 1997 Aug;112(2):538-40. No abstract available.
PMID: 9266897
Ko
CW, Bhandari B, Yee J, Terhune WC, Maldonado R, Kasinath BS.
Cyclic AMP regulates basement membrane heparan sulfate proteoglycan,
perlecan, metabolism in rat glomerular epithelial cells.
Mol Cell Biochem. 1996 Sep 6;162(1):65-73.
PMID: 8905627
Kasinath
BS.
Sifting the causes of microscopic hematuria.
Hosp Pract (Minneap). 1996 Jul 15;31(7):99-106, 109-10.
PMID: 8682891
Kasinath
BS, Grellier P, Choudhury GG, Abboud SL.
Regulation of basement membrane heparan sulfate proteoglycan, perlecan,
gene expression in glomerular epithelial cells by high glucose medium.
J Cell Physiol. 1996 Apr;167(1):131-6.
PMID: 8698830
Kasinath
BS.
Effect of insulin on high-glucose medium-induced changes in rat glomerular
epithelial cell metabolism of glycoconjugates.
Arch Biochem Biophys. 1995 Apr 20;318(2):286-94.
PMID: 7733656
Kasinath
BS, Block JA, Singh AK, Terhune WC, Maldonado R, Davalath S, Kallgren MJ,
Wanna L.
Regulation of rat glomerular epithelial cell proteoglycans by high-glucose
medium.
Arch Biochem Biophys. 1994 Feb 15;309(1):149-59.
PMID: 8117103
Singh
AK, Kasinath BS.
Metabolic fate of monovalent and multivalent antibodies of Heymann
nephritis following formation of surface immune complexes on glomerular
epithelial cells.
Clin Exp Immunol. 1993 Dec;94(3):403-11.
PMID: 8252800
Kasinath
BS.
Glomerular endothelial cell proteoglycans--regulation by TGF-beta 1.
Arch Biochem Biophys. 1993 Sep;305(2):370-7.
PMID: 8373175
Kasinath
BS, Fried TA, Davalath S, Marsden PA.
Glomerular epithelial cells synthesize endothelin peptides.
Am J Pathol. 1992 Aug;141(2):279-83.
PMID: 1497086
Kasinath
BS, Singh AK.
Detection of sialic acid on cultured cells by binding of a lectin from
Limax flavus.
J Am Soc Nephrol. 1992 Jul;3(1):113-5. No abstract available.
PMID: 1391703
Singh
AK, Kasinath BS, Lewis EJ.
Interaction of polycations with cell-surface negative charges of epithelial
cells.
Biochim Biophys Acta. 1992 Apr 17;1120(3):337-42.
PMID: 1576160
Levey
AS, Lan SP, Corwin HL, Kasinath BS, Lachin J, Neilson EG, Hunsicker LG,
Lewis EJ.
Progression and remission of renal disease in the Lupus Nephritis Collaborative
Study. Results of treatment with prednisone and short-term oral cyclophosphamide.
Ann Intern Med. 1992 Jan 15;116(2):114-23.
PMID: 1727614
Kasinath
BS.
Resident glomerular cells in glomerular injury: glomerular epithelial
cells.
Semin Nephrol. 1991 May;11(3):294-303. Review. No abstract available.
PMID: 2057644
Pugliese
F, Singh AK, Kasinath BS, Kreisberg JI, Lewis EJ.
Glomerular epithelial cell, polyanion neutralization is associated
with enhanced prostanoid production.
Kidney Int. 1987 Jul;32(1):57-61.
PMID: 3626300