Advances and challenges in kidney fibrosis therapeutics

Ong, K. L. et al. Global, regional, and national burden of diabetes from 1990 to 2021, with projections of prevalence to 2050: a systematic analysis for the Global Burden of Disease Study 2021. Lancet 402, 203–234 (2023).

Article  Google Scholar 

Sundström, J. et al. Prevalence, outcomes, and cost of chronic kidney disease in a contemporary population of 2·4 million patients from 11 countries: the CaReMe CKD study. Lancet Reg. Health Eur. 20, 100438 (2022).

Article  PubMed  PubMed Central  Google Scholar 

Boffa, J. J. et al. Angiotensin II activates collagen type I gene in the renal vasculature of transgenic mice during inhibition of nitric oxide synthesis: evidence for an endothelin-mediated mechanism. Circulation 100, 1901–1908 (1999).

Article  CAS  PubMed  Google Scholar 

Cho, J. J. et al. An oral endothelin-A receptor antagonist blocks collagen synthesis and deposition in advanced rat liver fibrosis. Gastroenterology 118, 1169–1178 (2000).

Article  CAS  PubMed  Google Scholar 

Li, L., Fu, H. & Liu, Y. The fibrogenic niche in kidney fibrosis: components and mechanisms. Nat. Rev. Nephrol. 18, 545–557 (2022).

Article  CAS  PubMed  Google Scholar 

Klingberg, F., Hinz, B. & White, E. S. The myofibroblast matrix: implications for tissue repair and fibrosis. J. Pathol. 229, 298–309 (2013).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Tanaka, S., Portilla, D. & Okusa, M. D. Role of perivascular cells in kidney homeostasis, inflammation, repair and fibrosis. Nat. Rev. Nephrol. 19, 721–732 (2023).

Article  PubMed  Google Scholar 

Huang, R., Fu, P. & Ma, L. Kidney fibrosis: from mechanisms to therapeutic medicines. Signal. Transduct. Target. Ther. 8, 1–20 (2023).

Google Scholar 

Kuppe, C. et al. Decoding myofibroblast origins in human kidney fibrosis. Nature 589, 281–286 (2021).

Article  CAS  PubMed  Google Scholar 

Cohen, C. et al. WNT-dependent interaction between inflammatory fibroblasts and FOLR2+ macrophages promotes fibrosis in chronic kidney disease. Nat. Commun. 15, 743 (2024).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Wu, L. et al. Peritubular capillary dysfunction and renal tubular epithelial cell stress following lipopolysaccharide administration in mice. Am. J. Physiol. Renal Physiol. 292, F261–F268 (2007).

Article  CAS  PubMed  Google Scholar 

Schrimpf, C., Teebken, O. E., Wilhelmi, M. & Duffield, J. S. The role of pericyte detachment in vascular rarefaction. J. Vasc. Res. 51, 247–258 (2014).

Article  PubMed  Google Scholar 

Ferenbach, D. A. & Bonventre, J. V. Mechanisms of maladaptive repair after AKI leading to accelerated kidney ageing and CKD. Nat. Rev. Nephrol. 11, 264–276 (2015).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Moretti, L., Stalfort, J., Barker, T. H. & Abebayehu, D. The interplay of fibroblasts, the extracellular matrix, and inflammation in scar formation. J. Biol. Chem. 298, 101530 (2022).

Article  CAS  PubMed  Google Scholar 

Tecklenborg, J., Clayton, D., Siebert, S. & Coley, S. M. The role of the immune system in kidney disease. Clin. Exp. Immunol. 192, 142 (2018).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Roumeliotis, S., Mallamaci, F. & Zoccali, C. Endothelial dysfunction in chronic kidney disease, from biology to clinical outcomes: a 2020 update. J. Clin. Med. 9, 2359 (2020).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Cao, Q., Harris, D. C. H. & Wang, Y. Macrophages in kidney injury, inflammation, and fibrosis. Physiol. Bethesda Md. 30, 183–194 (2015).

CAS  Google Scholar 

Henderson, N. C. et al. Galectin-3 expression and secretion links macrophages to the promotion of renal fibrosis. Am. J. Pathol. 172, 288–298 (2008).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Ryu, S. et al. Siglec-F-expressing neutrophils are essential for creating a profibrotic microenvironment in renal fibrosis. J. Clin. Invest. 132, e156876 (2022).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Shen, B., Liu, X., Fan, Y. & Qiu, J. Macrophages regulate renal fibrosis through modulating TGFβ superfamily signaling. Inflammation 37, 2076–2084 (2014).

Article  CAS  PubMed  Google Scholar 

Pardo, A. et al. Increase of lung neutrophils in hypersensitivity pneumonitis is associated with lung fibrosis. Am. J. Respir. Crit. Care Med. 161, 1698–1704 (2000).

Article  CAS  PubMed  Google Scholar 

Duffield, J. S. et al. Selective depletion of macrophages reveals distinct, opposing roles during liver injury and repair. J. Clin. Invest. 115, 56–65 (2005).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Gebru, Y. A. et al. T cell subsets and natural killer cells in the pathogenesis of nonalcoholic fatty liver disease. Int. J. Mol. Sci. 22, 12190 (2021).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Burfeind, K. G., Funahashi, Y., Munhall, A. C., Eiwaz, M. & Hutchens, M. P. Natural killer lymphocytes mediate renal fibrosis due to acute cardiorenal syndrome. Kidney360 5, 8–21 (2024).

Article  PubMed  Google Scholar 

Bonner, J. C. Regulation of PDGF and its receptors in fibrotic diseases. Cytokine Growth Factor Rev. 15, 255–273 (2004).

Article  CAS  PubMed  Google Scholar 

Biernacka, A., Dobaczewski, M. & Frangogiannis, N. G. TGF-β signaling in fibrosis. Growth Factors 29, 196–202 (2011).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Beljaars, L., Daliri, S., Dijkhuizen, C., Poelstra, K. & Gosens, R. WNT-5A regulates TGF-β-related activities in liver fibrosis. Am. J. Physiol. Gastrointest. Liver Physiol. 312, G219–G227 (2017).

Article  PubMed  Google Scholar 

Liu, J., Wang, F. & Luo, F. The role of JAK/STAT pathway in fibrotic diseases: molecular and cellular mechanisms. Biomolecules 13, 119 (2023).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Contreras, O. et al. Cross-talk between TGF-β and PDGFRα signaling pathways regulates the fate of stromal fibro-adipogenic progenitors. J. Cell Sci. 132, jcs232157 (2019).

Article  CAS  PubMed  Google Scholar 

Sun, Y., Zhang, Y. & Chi, P. Pirfenidone suppresses TGF-β1-induced human intestinal fibroblasts activities by regulating proliferation and apoptosis via the inhibition of the Smad and PI3K/AKT signaling pathway. Mol. Med. Rep. 18, 3907–3913 (2018).

CAS  PubMed  PubMed Central  Google Scholar 

Morimoto, Y. et al. TNF-ɑ deficiency accelerates renal tubular interstitial fibrosis in the late stage of ureteral obstruction. Exp. Mol. Pathol. 85, 207–213 (2008).

Article  CAS  PubMed  Google Scholar 

Widjaja, A. A. et al. Targeting endogenous kidney regeneration using anti-IL11 therapy in acute and chronic models of kidney disease. Nat. Commun. 13, 7497 (2022).

Article  CAS 

Comments (0)

No login
gif