TNF-α mediates obstruction-induced renal tubular cell apoptosis and proapoptotic signaling

Misseri, Rosalia; Meldrum, Daniel R.; Dinarello, Charles A.; Dagher, Pierre C.; Hile, Karen L.; Rink, Richard C.; Meldrum, Kirstan K.

doi:10.1152/ajprenal.00099.2004

Cited by 145 publications

(115 citation statements)

References 26 publications

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“…45 TNF-␣, FasL, and TWEAK have been successful therapeutic targets in AKI. 43,46,47 The requirement for cytokine cooperation to induce tubular cell death effectively underlies the observation that targeting individual cytokines has a therapeutic benefit. In addition, members of the TNF superfamily have a broad spectrum of nonlethal activities, including inflammation.…”

Section: Endogenous Promoters Of Apoptosismentioning

confidence: 99%

Mechanisms of Renal Apoptosis in Health and Disease

Sanz

Santamaría²,

Ruíz-Ortega³

et al. 2008

Journal of the American Society of Nephrology

236

192

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Section: Endogenous Promoters Of Apoptosismentioning

confidence: 99%

Mechanisms of Renal Apoptosis in Health and Disease

Sanz

Santamaría²,

Ruíz-Ortega³

et al. 2008

Journal of the American Society of Nephrology

236

192

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“…UUO appears to induce programmed cell death in renal tubular cells via activation of proapoptotic stimuli such as TNF-␣ (17) and TGF-␤ (16). This is accompanied by suppression of Bcl2 (4), dephosphorylation of BAD (15), activation of DAP kinase, and increased expression of the caspase cascade genes (26).…”

mentioning

confidence: 99%

PAX2 is reactivated in urinary tract obstruction and partially protects collecting duct cells from programmed cell death

Cohen¹,

Loutochin²,

Amin³

et al. 2007

American Journal of Physiology-Renal Physiology

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Obstruction of the urinary tract activates apoptotic pathways in collecting duct cells and leads to loss of renal parenchyma before surgical intervention. It has been suggested that developmental pathways may be reactivated to offset acute organ damage. One such molecule, PAX2, is expressed throughout the fetal collecting duct and was recently shown to suppress apoptosis during kidney development. We hypothesized that acute unilateral urinary tract obstruction (UUO) reactivates PAX2 expression in the mature kidney and partially suppresses apoptosis. If so, animals with PAX2 mutations should have increased susceptibility to parenchymal damage. Wild-type and heterozygous Pax2 mutant (C3H/ Pax2 1Neu) mice underwent unilateral ureteric ligation or sham operation at 6 wk of age; kidneys were examined after 5, 10, and 15 days. Whereas PAX2 protein levels fell to low levels in the first weeks of life, it was sharply reactivated by day 10 in collecting duct cells of wild-type but not in Pax2 1Neu mutant mice with UUO. Wild-type mice with UUO had marked TUNEL and cleaved spectrin staining in tubular cells and reduced kidney weight after 10–15 days. Mutant mice had exaggerated increases in markers of apoptosis and exaggerated loss of renal parenchymal loss in the obstructed kidney. These observations suggest that PAX2 is rapidly reactivated in UUO and that mice with genetically limited PAX2 expression have heightened susceptibility to apoptosis.

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“…22,23 Stretc hing of human tu bu lar cells in cre a ses the ir sus cep ti bi lity to TNF-α-in du ced apop to sis, which is cas pa se-de pendent. 24 An gi o ten sin II up re gu la tes TNF-in the rat kid ney with uni la te ral ure te ral obs truc ti on (UU -O).…”

Section: Discussionmentioning

confidence: 99%

Beneficial Effect of Doxazosin on Renal Apoptosis After Partial Bladder Outlet Obstruction

Kutlu¹,

Yalçinkaya²,

Elpek³

et al. 2010

Turkiye Klinikleri J Med Sci

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A AB BS S T TR RA AC CT T O Ob b j je ec c t ti i v ve e: : It is not known whet her in hi bi ti on of α1-ad re no re cep tor in a rat mo del of par ti al blad der out let obs truc ti on (BO O) ca u ses dec re a se in tu bu lar and glo me ru lar cell de ath by apop to sis and pre ven ti on of sub se qu ent inf lam ma ti on and fib ro sis. The aim of this study was to demons tra te the re la ti ons hip bet we en apop to sis and do xa zo si n   α1-ad re no cep tor an ta go nist) in rat kid neys da ma ged by par ti al BO O. M Ma a t te e r ri i a al l a an nd d M Me et t h ho od ds s: : A to tal of 45 adult fe ma le Wis tar rats,with a me an weight of 250 g we re ran domly al lo ca ted to four ex pe ri men tal gro ups as: sham-ope ra ted rats (10 rats), sham-ope ra ted rats tre a ted with do xa zo sin (10 rats), par ti al BO O gro up (14 rats), and parti al BO O gro up tre a ted with do xa zo sin (11 rats). Par ti al BO O was sur gi cally in du ced. De tec ti on of cell apop to sis was do ne by TU NEL as say. R Re e s su ul lt ts s: : This in ves ti ga ti on re ve a led in cre a sed apop to sis in both tu bu lar and glo me ru lar cells of rats with par ti al BO O. Furt her mo re, the re sults of this study de mons tra ted that do xa zo sin tre at ment of rats re du ced apop to sis in tu bu lar and glo me ru lar cells in both the con trols and the rats with par ti al BO O. C Co on nc c l lu u s si i o on n: : We be li e ve that our observation of dec re a sed apop to sis in both tu bu lar and glo me ru lar cells of rats with par ti al BO O might be use ful to ga in new in sight in to the the ra pe u tic ef fect of do xa zo sin.K Ke ey y W Wo or rd ds s: : Apoptosis; kidney; doxazosin Ö ÖZ ZE ET T A Am ma aç ç: : Me sa ne çı kış obs trük si yo nu (MÇO) oluş tu ru lan sı çan mo de lin de α1 ad re no re sep tör in hi bis yo nu nun apo pi to zis ile tü bü ler ve glo me rü ler hüc re ölü mü ne yol açıp aç ma dı ğı ve son rasın da ge li şen inf la mas yon ve fib ro zi si en gel le yip en gel le me di ği bi lin me mek te dir. Do la yı sıy la, bu ça -lış ma nın ama cı kıs mi MÇO ile ha sar lan dı rıl mış sı çan böb rek le rin de apo pi to zis ile dok sa zo sin (al fa 1 re sep tör an ta go nis ti) ara sın da ki iliş ki yi gös ter mek tir. G Ge e r re eç ç v ve e Y Yö ön n t te em m l le er r: : Or ta la ma 250 gram ağır lı ğın da ki top lam 45 adet di şi Wis tar sı çan la rı 4 de ney sel gru ba ran do mi ze edil di: sham ope rasyon lu sı çan lar (10 sı çan), dok sa zo sin ile te da vi edi len sham ope ras yon lu sı çan lar (14 sı çan), kıs mi MÇO gru bu (14 sı çan), ve dok sa zo sin ile te da vi edi len kıs mi MÇO gru bu. Sı çan lar da ki kıs mi MÇO cer ra hi ola rak in dük len di. Hüc re apo pi to zi si TU NEL ana li zi tes pit edil di. B Bu ul l g gu u l la ar r: : Bu araş tır ma kıs mi MÇO' lu sı çan lar da hem tü bü ler hem de glo me rü ler hüc re ler de art mış apo pi to zi si gös ter miş -tir. Ay rı ca, bu ça lış ma nın so nuç la rı dok sa zo si nin kıs mi MÇO' lu sı çan lar da ve kon trol gru bu nu oluş-tu ran sı ça...

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TNF-α mediates obstruction-induced renal tubular cell apoptosis and proapoptotic signaling

Cited by 145 publications

References 26 publications

Mechanisms of Renal Apoptosis in Health and Disease

Mechanisms of Renal Apoptosis in Health and Disease

PAX2 is reactivated in urinary tract obstruction and partially protects collecting duct cells from programmed cell death

Beneficial Effect of Doxazosin on Renal Apoptosis After Partial Bladder Outlet Obstruction

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