Deletion of β1-integrin in collecting duct principal cells leads to tubular injury and renal medullary fibrosis

Fahmy A. Mamuya, Dongping Xie, Lei Lei, Ming Huang, Kenji Tsuji, Diane E. Capen, Baoxue Yang, Ralph Weissleder, Teodor G. Păunescu, Hua A. Jenny Lu

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

The renal collecting duct (CD) contains two major cell types, intercalated (ICs) and principal cells (PCs). A previous report showed that deletion of β1-integrin in the entire renal CD causes defective CD morphogenesis resulting in kidney dysfunction. However, subsequent deletion of β1-integrin specifically in ICs and PCs, respectively, did not cause any morphological defects in the CDs. The discrepancy between these studies prompts us to reinvestigate the role of β1-integrin in CD cells, specifically in the PCs. We conditionally deleted β1-integrin in mouse CD PCs using a specific aquaporin-2 (AQP2) promoter Cre-LoxP system. The resulting mutant mice, β-1f/fAQP2-Cre+, had lower body weight, failed to thrive, and died around 8-12 wk. Their CD tubules were dilated, and some of them contained cellular debris. Increased apoptosis and proliferation of PCs were observed in the dilated CDs. Trichrome staining and electron microscopy revealed the presence of peritubular and interstitial fibrosis that is associated with increased production of extracellular matrix proteins including collagen type IV and fibronectin, as detected by immunoblotting. Further analysis revealed a significantly increased expression of transforming growth factor- β (TGF- β)-induced protein, fibronectin, and TGF-β receptor-1 mRNAs and concomitantly increased phosphorylation of SMAD-2 that indicates the activation of the TGF- β signaling pathway. Therefore, our data reveal that normal expression of β1-integrin in PCs is a critical determinant of CD structural and functional integrity and further support the previously reported critical role of β1-integrin in the development and/or maintenance of the CD structure and function.

Original languageEnglish
Pages (from-to)F1026-F1037
JournalAmerican Journal of Physiology - Renal Physiology
Volume313
Issue number4
DOIs
Publication statusPublished - Oct 9 2017
Externally publishedYes

Fingerprint

Integrins
Fibrosis
Kidney
Wounds and Injuries
Transforming Growth Factors
Fibronectins
Aquaporin 2
Collagen Type IV
Growth Factor Receptors
Extracellular Matrix Proteins
Morphogenesis
Immunoblotting
Electron Microscopy
Body Weight
Maintenance
Phosphorylation
Cell Proliferation
Apoptosis
Staining and Labeling
Messenger RNA

Keywords

  • Aquaporin-2
  • Collecting ducts
  • Renal fibrosis
  • TGF-β
  • β1-integrins

ASJC Scopus subject areas

  • Physiology
  • Urology

Cite this

Deletion of β1-integrin in collecting duct principal cells leads to tubular injury and renal medullary fibrosis. / Mamuya, Fahmy A.; Xie, Dongping; Lei, Lei; Huang, Ming; Tsuji, Kenji; Capen, Diane E.; Yang, Baoxue; Weissleder, Ralph; Păunescu, Teodor G.; Jenny Lu, Hua A.

In: American Journal of Physiology - Renal Physiology, Vol. 313, No. 4, 09.10.2017, p. F1026-F1037.

Research output: Contribution to journalArticle

Mamuya, FA, Xie, D, Lei, L, Huang, M, Tsuji, K, Capen, DE, Yang, B, Weissleder, R, Păunescu, TG & Jenny Lu, HA 2017, 'Deletion of β1-integrin in collecting duct principal cells leads to tubular injury and renal medullary fibrosis', American Journal of Physiology - Renal Physiology, vol. 313, no. 4, pp. F1026-F1037. https://doi.org/10.1152/ajprenal.00038.2017
Mamuya, Fahmy A. ; Xie, Dongping ; Lei, Lei ; Huang, Ming ; Tsuji, Kenji ; Capen, Diane E. ; Yang, Baoxue ; Weissleder, Ralph ; Păunescu, Teodor G. ; Jenny Lu, Hua A. / Deletion of β1-integrin in collecting duct principal cells leads to tubular injury and renal medullary fibrosis. In: American Journal of Physiology - Renal Physiology. 2017 ; Vol. 313, No. 4. pp. F1026-F1037.
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AU - Huang, Ming

AU - Tsuji, Kenji

AU - Capen, Diane E.

AU - Yang, Baoxue

AU - Weissleder, Ralph

AU - Păunescu, Teodor G.

AU - Jenny Lu, Hua A.

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