Thyroid Hormones Stimulate Renal Expression of &lt;i&gt;CFTR&lt;/i&gt;

Pinto, Ana C.O. de Andrade; Barbosa, Carolina; Ornellas, Débora S.; Novaira, Horacio J.; Souza-Menezes, Jackson; Ortiga-Carvalho, Tânia M.; Fong, Peter; Morales, Marcelo M.

doi:10.1159/000104156

Cited by 9 publications

(9 citation statements)

References 40 publications

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“…The technique was chosen for comparison of renal mRNA expression for each studied gene in experimental animals compared to control group (SHAM, taken as 100% [19]). Firststrand complementary deoxyribonucleic acid (cDNA) was prepared using 1 µg of total RNA.…”

Section: Semi-quantitative Reverse Transcription and Polymerase Chainmentioning

confidence: 99%

Bone Marrow Mononuclear Cells Attenuate Interstitial Fibrosis and Stimulate the Repair of Tubular Epithelial Cells after Unilateral Ureteral Obstruction

Barreira

Takiya²,

Castiglione

et al. 2009

Cell Physiol Biochem

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The growing number of patients suffering from chronic renal disease is a challenge for the development of innovative therapies. Benefits of cell therapy in acute renal diseases in animal models have been reported but seldom for chronic lesions. We present evidence for the improvement of renal morphology in a model of tubulointerstitial fibrosis. Wistar rats were submitted to unilateral ureteral obstruction (UUO), treated with bone-marrow mononuclear cells (UUO+BMMC) infused via the cava vein, and killed on day 14. Labeled BMMC were seen in renal tissue after 7 days in the group UUO+BMMC. UUO+BMMC also showed a reduction in ED1⁺ cells and tubular apoptotic cells together with enhanced tubular proliferation. Myofibroblasts were also reduced after BMMC which is consistent with a decrease in collagen deposition (picro Sirius staining) and RT-PCR data showing lower levels of procollagen-I mRNA. Simultaneously, nestin+ cells increased in the interstitium and decreased in the tubules. Double stained nestin⁺/α-SMA⁺ cells were present only in the interstitium, and their levels did not change after BMMC infusion. These data indicate a renoprotective effect of BMMC through increased tubular cell regeneration, inhibition of tubular cell apoptosis and partially blocking of the inflammatory and fibrotic events that occur after unilateral ureteral obstruction.

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Section: Semi-quantitative Reverse Transcription and Polymerase Chainmentioning

confidence: 99%

Bone Marrow Mononuclear Cells Attenuate Interstitial Fibrosis and Stimulate the Repair of Tubular Epithelial Cells after Unilateral Ureteral Obstruction

Barreira

Takiya²,

Castiglione

et al. 2009

Cell Physiol Biochem

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“…Once CFTR is abundantly expressed in kidneys (Souza-Menezes et al 2008;de Andrade Pinto et al 2007a;Morales et al 2001;Morales et al 1996Morales et al , 2000, is there an important function for this transporter in renal physiology? Is there an interaction of CFTR with other transporters expressed in renal epithelia?…”

Section: Structure and Function Of Cftrmentioning

confidence: 99%

“…Indeed, the thyroid hormones, thyroxine (T4) and triiodothyronine (T3), affect renal morphology as well as the activity of ion transporters via alteration of their function and/or expression along the nephron (de Andrade Pinto et al 2007b). Thus, depending on their plasma levels, THs can regulate renal NaCl excretion (Azuma et al 1996).…”

Section: Cftr Expression Regulation By Hormones Involved In Extracellmentioning

confidence: 99%

CFTR structure and function: is there a role in the kidney?

Souza-Menezes

Morales

2009

Biophys Rev

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Cystic fibrosis (CF) is a lethal autosomal recessive genetic disease caused by mutations in the CF transmembrane conductance regulator (CFTR). Mutations in the CFTR gene may result in a defective protein processing that leads to changes in function and regulation of this chloride channel. Despite of the expression of CFTR in the kidney, patients with CF do not present major renal dysfunction, but it is known that both the urinary excretion of proteins and renal capacity to concentrate and dilute urine are altered in these patients. CFTR mRNA is expressed in all nephron segments of rat and human, and this abundance is more prominent in renal cortex and outer medulla renal areas. CFTR protein was detected in apical surface of both proximal and distal tubules of rat kidney but not in the outer medullary collecting ducts. Studies have demonstrated that CFTR does not only transport Cl but also ATP. ATP transport by CFTR could be involved in the control of other ion transporters such as Na (ENaC) and K (renal outer medullary potassium) channels, especially in TAL and CCD. In the kidney, CFTR also might be involved in the endocytosis of low-molecular-weight proteins by proximal tubules. This review is focused on the CFTR function and structure, its role in the renal physiology, and its modulation by hormones involved in the control of extracellular fluid volume.

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“…This similar pattern of expression of ClC-2 mRNA and protein found for homozygous and heterozygous mice in kidney could be secondary to a a phenomenon called dominant negative regulation by the mutant receptor, in which the mutant thyroid hormone receptor interferes with the function of the normal receptor in the regulation of target genes [33]. The dysfunction of TR-β receptor can also interfere with other chloride transporters such as the chloride channel CFTR [34]. This channel is a modulator of other transporters, including sodium and chloride, and could contribute to the reduction in FE Na and FE Cl observed in our results [35] (Table 1).…”

Section: Discussionmentioning

confidence: 70%

Thyroid Hormone Beta Receptor Mutation Causes Renal Dysfunction and Impairment of ClC-2 Chloride Channel Expression in Mouse Kidney

Santos¹,

Gomes²,

Santiago

et al. 2010

Cell Physiol Biochem

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Background/Aims: Mutations in the thyroid hormone receptor β (TR-β) gene result in resistance to thyroid hormone (RTH). Mutation Δ337T in the TR-β gene has been shown to have the characteristics of RTH syndrome in mice. The aim of this work was to study the possible involvement of TR-β receptor in thyroid modulation of ClC-2 in mouse kidney. Methods: Expression of mouse (Δ337T and normal C57BL/6) renal RNA and protein expression were studied by reverse transcriptase-polymerase chain reaction and Western blot, respectively, in mice with hyper- or hypothyroidism. Renal function was studied by analysis of urinary electrolyte excretion. Studies of the ClC-2 promoter region were performed in immortalized renal proximal tubule (IRPT) cells. Results: In RTH syndrome mice (Δ337T), renal dysfunction was found to be associated with changes in the fractional excretion of sodium (FE_Na) and chloride (FE_Cl). ClC-2 chloride channel mRNA and protein expression were found to be decreased by 40% in heterozygous and homozygous mutant mouse kidneys and high levels of plasma thyroid hormone were detected in both groups. Hypothyroidism induced by methimazole decreased the renal expression of ClC-2 in normal mice but not in Δ337T mutant mice. In in vitro studies performed on IRPT cells subjected to thyroid hormone treatment, the promoter region of the ClC-2 chloride channel was stimulated in a dose-dependent manner. Conclusions: This work emphasizes the importance of thyroid hormone in electrolyte handling along the nephron and suggests its participation in renal ClC-2 gene transcription via the TR-β receptor pathway.

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Thyroid Hormones Stimulate Renal Expression of <i>CFTR</i>

Cited by 9 publications

References 40 publications

Bone Marrow Mononuclear Cells Attenuate Interstitial Fibrosis and Stimulate the Repair of Tubular Epithelial Cells after Unilateral Ureteral Obstruction

Bone Marrow Mononuclear Cells Attenuate Interstitial Fibrosis and Stimulate the Repair of Tubular Epithelial Cells after Unilateral Ureteral Obstruction

CFTR structure and function: is there a role in the kidney?

Thyroid Hormone Beta Receptor Mutation Causes Renal Dysfunction and Impairment of ClC-2 Chloride Channel Expression in Mouse Kidney

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